Everand Logo

Welcome to Everand!

  • Discover millions of ebooks, audiobooks, and so much more with a free trial

    Only $11.99/month after trial. Cancel anytime.

    The Complement FactsBook
    The Complement FactsBook
    The Complement FactsBook
    Ebook1,247 pages9 hours

    The Complement FactsBook

    ()

    Read preview

    About this ebook

    The Complement FactsBook, Second Edition, provides in-depth insights and an overview of the components of the complement system. This new edition highlights the use of newly recommended complement nomenclature, covering new pathways and proteins and adding information on mouse homologs. It is a completely revised and updated edition containing entries on all components of the complement system, and is an excellent source of one-stop shopping for complement information and references. It is the most convenient compilation of biochemical, biological and molecular biology for complementologists and those new in the field.

    This new edition is expanded to include relevant updates and topics that have evolved since the last edition was published, including C1q and Lectins, C3 Family, Serine Proteases, Serum Regulators of Complement Activation, Cell Surface Proteins, and Terminal Pathway Proteins. Domain Structure diagrams are incorporated to clearly illustrate the relationships between all the complement proteins, both within families and between families.

    • Introduces complement function, simply described for each function
    • Includes the cDNA sequences that are marked with intron/exon boundaries, facilitating genetic studies
    • Presents detailed structural information, including cDNA and gene structure for all proteins
    • Incorporates domain structures diagrams, which beautifully illustrate the relationship between all the complement proteins, both within, and between, families
    LanguageEnglish
    PublisherAcademic Press
    Release dateOct 19, 2017
    ISBN9780128104217
    The Complement FactsBook

    Related to The Complement FactsBook

    Titles in the series (17)

    View More
    View More

    Related ebooks

    Biology For You

    View More
    View More

    Related podcast episodes

    Related articles

    • Article

      What Defines a Stem Cell?

      Dec 27, 2018

      For the past three years, researchers at the Hubrecht Institute in the Netherlands have been painstakingly cataloging and mapping all the proliferating cells found in mouse hearts, looking for cardiac stem cells. The elusive cells should theoreticall

      5 min read

    • Article

      With the Nobel Prizes Around the Corner, It’s Crystal Ball Time

      Sep 25, 2017

      The scientists who pioneered immunotherapy and other cancer advances are among the favorites for this year's Nobel Prizes, which will be announced the first week of October.

      4 min read

    • Article

      This Gene Mutation Causes Some Repeat Miscarriages

      Aug 17, 2018

      A couple’s tragic miscarriages have led to the discovery of a gene mutation underlying hydrops fetalis—a fatal condition to fetuses due to fluid buildup in the space among organs. The proteins at the center of this finding have already been implicate

      3 min read

    • Article

      For Better Diagnosis, Watch Proteins Fold In Real-time

      Jun 10, 2018

      10A new method can examine protein assembly in real time, in living cells, to find problems in the process and diagnose the resulting diseases, according to new research. Proteins in the body need to be perfectly arranged, or folded, to do their jobs

      2 min read

    • Article

      How Cells Do ‘Quality Control’ For Misfolded Proteins

      Dec 7, 2018

      Researchers have identified the key molecular players in the decisions cells make about whether to scrap or salvage misfolded proteins. Proteins are the workhorses of our cells, carrying out essential tasks to keep our cells—and our bodies—functionin

      2 min read

    • Article

      Malaria Parasite Packs Bags To Travel From Host To Host

      Mar 1, 2018

      The parasite that causes malaria has not one, but two, specialized proteins that protect its messenger RNA—genetic material that encodes for proteins—until the parasite takes up residence in a new mosquito or a human host, researchers report. A new s

      3 min read

    • Article

      Compound Targets ‘Undruggable’ Prostate Cancer Cells

      Oct 23, 2018

      A new type of molecule blocks the action of genes that drive the growth of therapy-resistant prostate cancer, according to a new study. “Rather than continue making compounds that are just like older drugs, the focus of our work has been to rethink t

      3 min read

    • Article

      The Dangerous Evolution of the Coronavirus

      Jan 27, 2021

      Relief coursed through me last week when I learned my 2-year-old daughter’s daycare provider got her first dose of the Pfizer vaccine. It left her feeling more groggy than she expected, but that was a good thing, suggesting the vaccine was kicking he

      6 min read

    • Article

      New Method Identifies The Proteins That Unpack DNA

      Jul 13, 2018

      A new method makes it possible to systematically identify specialized proteins that unpack DNA inside the nucleus of a cell, making the usually dense DNA more accessible for gene expression and other functions. The method, and the shared characterist

      2 min read

    • Article

      Fruit Fly Stem Cells Offer Glimpse Of ‘Perpetual Life’

      Feb 14, 2018

      Researchers have discovered that sperm-producing fruit fly stem cells use a genetic trick to stay perpetually young across generations. Certain sections of the fruit fly genome get shorter with age, but, remarkably, some reproductive cells can repair

      2 min read

    • Article

      New Way To Study Protein Complexes Doesn’t Break Them Up

      Mar 23, 2018

      Researchers have developed a new way to study protein complexes. Proteins are the worker bees of the cell, mainly ganging up to form macromolecular, multicomponent complexes to perform intricate cellular tasks. “Proteins are the main drivers of prett

      2 min read

    • Article

      Mutant ‘Neighbor’ Gene Causes Rare Inability To Process B12

      Jan 31, 2018

      Researchers have discovered a new cause of a rare condition known as cblC, in which patients can’t process vitamin B12, leading to severe health problems. They report the condition, which they named “epi-cblC,” in patients from Europe and the United

      3 min read

    Related categories

    Reviews for The Complement FactsBook

    0 ratings

    0 ratings0 reviews

    What did you think?

    Tap to rate

    Review must be at least 10 words

      Book preview

      The Complement FactsBook - Scott R. Barnum

      The Complement FactsBook

      Second Edition

      Editors

      Scott Barnum

      Theresa Schein

      Table of Contents

      Cover image

      Title page

      Copyright

      List of Contributors

      Preface

      Chapter 1. Introduction

      Aims and Scope of the Book

      Organisation of the Data

      Chapter 2. The Complement System

      Historical Perspective

      Modular Structure of the Components

      Pathways

      Part I. Collectins

      Chapter 3. C1q

      Physicochemical Properties

      Structure

      Function

      Degradation Pathway

      Tissue Distribution

      Regulation of Expression

      Human Protein Sequence

      Protein Modules

      Chromosomal Location

      Human cDNA Sequence

      Genomic Structure

      Accession Numbers

      Deficiency

      Polymorphic Variants

      Mutant Animals

      Chapter 4. Mannose-Binding Lectin

      Other Names of Mannose-Binding Lectin

      Physicochemical Properties

      Structure

      Function

      Tissue Distribution

      Regulation of Expression

      Protein Sequence

      Protein Modules

      Chromosomal Location

      cDNA Sequence

      Genomic Structure

      Accession Numbers

      Deficiency

      Polymorphic Variants

      Mutant Animals

      Chapter 5. Ficolins

      Other Names for Ficolins

      Physicochemical Properties

      Ficolin-1

      Ficolin-2

      Ficolin-3

      Structure

      Function

      Tissue Distribution

      Protein Sequence

      Protein Modules

      Chromosomal Location

      cDNA Sequence

      Genomic Structure

      Accession Numbers

      Deficiency

      Polymorphic Variants

      Ficolin-Deficient Mouse

      Chapter 6. The Collectins

      Other Names

      Physicochemical Properties

      Structure

      Crystal Structure

      Function

      Tissue Distribution

      Regulation of Expression

      Human Protein Sequence

      Protein Modules

      Chromosomal Location

      Human cDNA Sequence

      Genomic Structure

      Accession Numbers

      Deficiency

      Polymorphic Variants

      Mutant Animals

      Part II. Serine Proteases

      Chapter 7. MASP-1

      Physicochemical Properties

      Structure

      Function

      Tissue Distribution

      Regulation of Expression

      Human Protein Sequence

      Protein Modules

      Chromosomal Location

      Human cDNA Sequence

      Genomic Structure

      Accession Numbers

      Deficiency

      Polymorphic Variants

      Mutant Animals

      Chapter 8. MASP-2

      Physicochemical Properties

      Structure

      Function

      Tissue Distribution

      Regulation of Expression

      Human Protein Sequence

      Protein Modules

      Chromosomal Location

      Human cDNA Sequence

      Genomic Structure

      Accession Numbers

      Deficiency

      Polymorphic Variants

      Mutant Animals

      Chapter 9. MASP-3

      Physicochemical Properties

      Structure

      Function

      Tissue Distribution

      Regulation of Expression

      Human Protein Sequence

      Protein Modules

      Chromosomal Location

      Human cDNA Sequence

      Genomic Structure

      Accession Numbers

      Deficiency

      Polymorphic Variants

      Mutant Animals

      Chapter 10. C1r

      Physicochemical Properties

      Structure

      3D Structure

      Function

      Tissue Distribution

      Regulation of Expression

      Human Protein Sequence

      Protein Modules

      Chromosomal Location

      Human cDNA Sequence

      Genomic Structure

      Accession Numbers

      Deficiency

      Polymorphic Variants

      Mutant Animals

      Chapter 11. C1s

      Physicochemical Properties

      Structure

      3D Structure

      Function

      Tissue Distribution

      Regulation of Expression

      Human Protein Sequence

      Protein Modules

      Chromosomal Location

      Human cDNA Sequence

      Genomic Structure

      Accession Numbers

      Deficiency

      Polymorphic Variants

      Mutant Animals

      Chapter 12. Factor D

      Other Names

      Physicochemical Properties

      Structure

      Function

      Degradation Pathway

      Tissue Distribution

      Regulation of Expression

      Human Protein Sequence

      Protein Modules

      Chromosomal Location

      cDNA Sequences

      Genomic Structure

      Accession Numbers

      Deficiency

      Polymorphic Variants

      Mutant Animals

      Chapter 13. C2

      Physiochemical Properties

      Structure

      Function

      Tissue Distribution

      Expression and Regulation

      Protein Sequence

      Protein Modules

      Chromosomal Location

      cDNA Sequence

      Genomic Structure

      Accession Numbers

      Deficiency

      Polymorphic Variants

      Mutant Animals

      Chapter 14. Factor B

      Other Names

      Physicochemical Properties

      Structure

      Function

      Tissue Distribution

      Regulation of Expression

      Protein Sequences

      Protein Modules

      Chromosomal Location

      cDNA Sequence

      Genomic Structure

      Accession Numbers

      Deficiency

      Polymorphic Variants

      Mutant Animals

      Chapter 15. Factor I

      Other Names

      Physicochemical Properties

      Structure

      Function

      Tissue Distribution

      Regulation of Expression

      Protein Sequences

      Protein Modules

      Chromosomal Location

      cDNA Sequences and Genomic Structure

      Polymorphic Variants, Deficiency and Disease-Related Single Nucleotide Polymorphisms

      FI Knockout Mice

      Part III. C3 Family

      Chapter 16. C3

      Physicochemical Properties

      Structure

      Function

      Degradation Pathway

      Tissue Distribution

      Regulation of Expression

      Human Protein Sequence

      Protein Modules

      Chromosomal Location

      Human cDNA Sequence

      Genomic Structure

      Accession Numbers

      Deficiency

      Polymorphic Variants

      Mutant Animals

      Chapter 17. C4

      Other Names

      Physicochemical Properties

      Structure

      Function

      Tissue Distribution

      Regulation of Expression

      Protein Sequence

      Protein Modules

      Chromosomal Location

      cDNA Sequence

      Genomic Structure

      Accession Numbers

      Deficiency

      Polymorphic Variants

      Mutant Animals

      C4 Knockout Mouse Phenotypes

      Chapter 18. C5

      Other Names

      Physicochemical Properties

      Structure

      Function

      Degradation Pathway

      Tissue Distribution

      Regulation of Expression

      Human Protein Sequence

      Protein Modules

      Chromosomal Location

      Human cDNA Sequence

      Accession Numbers

      Deficiency

      Polymorphic Variants

      Mutant Animals

      Part IV. Terminal Pathway Components

      Chapter 19. C6

      Physiochemical Properties

      Structure

      Function

      Tissue Distribution

      Regulation of Expression

      Human Protein Sequence

      Chromosomal Location

      Human cDNA Sequence

      Genomic Structure

      Accession Numbers

      Deficiency

      Polymorphic Variants

      Mutant Animals

      Chapter 20. C7

      Physiochemical Properties

      Structure

      Function

      Tissue Distribution

      Regulation of Expression

      Human Protein Sequence

      Chromosomal Location

      Human cDNA Sequence

      Genomic Structure

      Accession Numbers

      Deficiency

      Polymorphic Variants

      Mutant Animals

      Chapter 21. C8

      Physiochemical Properties

      Structure

      Crystal Structures

      Function

      Tissue Distribution

      Regulation of Expression

      Human Protein Sequence

      Chromosomal Location

      Human cDNA Sequence

      Genomic Structure

      Accession Numbers

      Deficiency

      Mutant Animals

      Chapter 22. C9

      Physicochemical Properties

      Structure

      Function

      Tissue Distribution

      Regulation of Expression

      Human Protein Sequence

      Protein Modules

      Chromosomal Location

      Human cDNA Sequence

      Genomic Structure

      Accession Numbers

      Deficiency

      Polymorphic Variants

      Mutant Animals

      Part V. Regulatory Proteins

      Chapter 23. C1 Inhibitor

      Physicochemical Properties

      Structure

      Functions

      Degradation Pathway

      Tissue Distribution

      Regulation of Expression

      Human Protein Sequence

      Protein Modules

      Chromosomal Location

      cDNA Sequence

      Genomic Structure

      Deficiency

      Polymorphic Variants

      Mutant Animals

      Chapter 24. C4b-Binding Protein

      Other Names

      Physicochemical Properties

      Structure

      Function

      Tissue Distribution

      Regulation of Expression

      Protein Sequences

      Protein Modules

      Chromosomal Location and Genomic Structure

      cDNA Sequences

      Deficiency

      Polymorphic Variants and Disease-Related Single Nucleotide Polymorphisms

      C4BP Knockout and Transgenic Mice

      Chapter 25. Decay-Accelerating Factor

      Physiochemical Properties

      Structure

      Function

      Tissue Distribution

      Regulation of Expression

      Protein Sequence

      Protein Modules

      Chromosomal Location

      cDNA Sequence

      Exon 10

      Genomic Structure

      Accession Numbers (EMBL/GenBank)

      Deficiency

      Polymorphic Variants

      Mutant Animals

      Chapter 26. Membrane Cofactor Protein

      Other Names

      Physicochemical Properties

      Structure

      Function

      Tissue Distribution

      Regulation of Expression

      Human Protein Sequence

      Protein Modules

      Chromosomal Location

      Human cDNA Sequence (ABC1)

      Genomic Structure

      Accession Numbers

      Deficiency/Diseases

      Polymorphic Variants

      Mutant Animals

      Chapter 27. Properdin

      Physiochemical Properties

      Structure

      Function

      Tissue Distribution

      Regulation of Expression

      Human Protein Sequence

      Protein Modules

      Chromosomal Location

      Human cDNA Sequence

      Genomic Structure

      Accession Numbers

      Deficiency

      Polymorphic Variants

      Mutant Animals

      Chapter 28. CR1

      Other Names

      Physicochemical Properties

      Structure

      Function

      Tissue Distribution

      Regulation of Expression

      Protein Sequence

      Protein Modules

      Ligand Binding Sites

      Protein–Protein Interaction Sites

      Chromosomal Location

      Human cDNA Sequence

      Genomic Structure

      Accession Numbers

      Deficiency

      Polymorphic Variants

      Polymorphism Frequencies

      Mutant Animals

      Chapter 29. CRIg

      Other Names

      Physicochemical Properties

      Structure

      Function

      Tissue Distribution

      Regulation of Expression

      Human Protein Sequence

      Protein Modules

      Chromosomal Localisation

      cDNA Sequence

      Genomic Structure

      Accession Numbers

      Deficiency and Polymorphic Variants

      Deficient Mice

      Chapter 30. Factor H and Factor H-like Protein 1

      Other Names

      Physicochemical Properties

      Structure

      Function

      Tissue Distribution

      Regulation of Expression

      Human Protein Sequence

      Protein Modules

      Chromosomal Location

      Human cDNA Sequence

      Genomic Structure

      Accession Numbers

      Deficiency

      Polymorphic Variants

      Mutant Animals

      Chapter 31. Factor H-Related Proteins 1–5

      Other Names

      Physicochemical Properties

      Structure

      Function

      Tissue Distribution

      Regulation of Expression

      Protein Modules

      Chromosomal Location

      Genomic Structure

      Deficiency

      Polymorphic Variants

      Mutant Animals

      Chapter 32. Clusterin

      Other Names

      Physicochemical Properties

      Structure

      Function

      Tissue Distribution

      Regulation of Expression

      Protein Sequence

      Protein Modules

      Chromosomal Location

      cDNA Sequence

      Genomic Structure

      Accession Numbers

      Deficiency

      Polymorphic Variants

      Mutant Animals

      Chapter 33. Vitronectin

      Other Names

      Physicochemical Properties

      Structure

      Function

      Degradation Pathway

      Tissue Distribution

      Regulation of Expression

      Human Protein Sequence

      Protein Modules

      Chromosomal Location

      cDNA Sequence

      Genomic Structure

      Accession Numbers

      Deficiency

      Polymorphic Variants

      Mutant Animals

      Chapter 34. CD59

      Physicochemical Properties

      Structure

      Function

      Tissue Distribution

      Regulation of Expression

      Human Protein Sequence

      Chromosomal Location

      Human cDNA Sequence

      Genomic Structure

      Accession Numbers

      Deficiency

      Polymorphic Variants

      Mutant Animals

      Chapter 35. CSMD1

      Other Names

      Physicochemical Properties

      Structure

      Function

      Degradation Pathway

      Tissue Distribution

      Regulation of Expression

      Human Protein Sequence

      Protein Modules

      Chromosomal Location

      Human cDNA Sequence

      Genomic Structure

      Accession Numbers

      Deficiency

      Polymorphic Variants

      Mutant Animals

      Part VI. Anaphylatoxin and Leucocyte Receptors

      Chapter 36. C3aR1

      Other Names

      Physiochemical Properties

      Structure

      Function

      Tissue Distribution

      Regulation of Expression

      Human Protein Sequence

      Protein Modules

      Chromosomal Location

      Human cDNA Sequence

      Genomic Structure

      Accession Numbers

      Deficiency

      Polymorphic Variants

      Mutant Animals

      Chapter 37. C5aR1

      Other Names

      Physiochemical Properties

      Structure

      Function

      Tissue Distribution

      Regulation of Expression

      Human Protein Sequence

      Protein Modules

      Chromosomal Location

      Human cDNA Sequence

      Genomic Structure

      Accession Numbers

      Deficiency

      Polymorphic Variants

      Mutant Animals

      Chapter 38. C5aR2

      Other Names

      Physiochemical Properties

      Structure

      Function

      Tissue Distribution

      Regulation of Expression

      Human Protein Sequence

      Protein Modules

      Chromosomal Location

      Human cDNA Sequence

      Genomic Structure

      Accession Numbers

      Deficiency

      Polymorphic Variants

      Mutant Animals

      Chapter 39. C1q Receptors

      Introduction

      Calreticulin (cC1q-R, Collectin Receptor, CR)

      gC1qR (p33, p32, C1qBP, TAP)

      CD93 (Originally Identified as C1qRP)

      Complement Receptor 1 (CR1, CD35)

      α2β1 (Very Late Antigen-1/VLA-2, GPIa-IIa, ITGA2, CD49B)

      LDL-Receptor Related Protein-1 (LRP-1, CD91 or α2-Macroglobulin Receptor)

      Receptor for Advanced Glycation End-Products (RAGE, AGER)

      Leucocyte-Associated Immunoglobulin-Like Receptor-1 (LAIR-1, CD305)

      Scavenger Receptor Type-Family Member 1 (SCARF1, Originally Described as Scavenger Receptor Expressed by Endothelial Cells-1, SREC-1)

      Multiple epidermal growth factor-Like Domains 10 (Megf10, Scavenger Receptor Type F- 3/SR-F3)

      Chapter 40. CR2

      Other Names

      Physicochemical Properties

      Structure

      Function

      Tissue Distribution

      Regulation of Expression

      Human Protein Sequence

      Protein Modules

      Chromosomal Location

      Human cDNA Sequence

      Genomic Structure

      Accession Numbers

      Deficiency

      Polymorphic Variants

      Mutant Animals

      Chapter 41. CR3

      Other Names

      Physicochemical Properties

      Structure

      Function

      Tissue Distribution

      Regulation of Expression

      Human Protein Sequence

      Protein Modules

      Chromosomal Location

      Human cDNA Sequence

      Genomic Structure

      Accession Numbers

      Deficiency

      Polymorphic Variants

      Mutant Animals

      Chapter 42. CR4

      Other Names

      Physicochemical Properties

      Structure

      Function

      Tissue Distribution

      Regulation of Expression

      Human Protein Sequence

      Protein Modules

      Chromosomal Location

      Human cDNA Sequence

      Genomic Structure

      Accession Numbers

      Deficiency

      Polymorphic Variants

      Mutant Animals

      Appendix A. Complement Nomenclature 2014

      Index

      Copyright

      Academic Press is an imprint of Elsevier

      125 London Wall, London EC2Y 5AS, United Kingdom

      525 B Street, Suite 1800, San Diego, CA 92101-4495, United States

      50 Hampshire Street, 5th Floor, Cambridge, MA 02139, United States

      The Boulevard, Langford Lane, Kidlington, Oxford OX5 1GB, United Kingdom

      Copyright © 2018 Elsevier Ltd. All rights reserved.

      No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without permission in writing from the publisher. Details on how to seek permission, further information about the Publisher’s permissions policies and our arrangements with organizations such as the Copyright Clearance Center and the Copyright Licensing Agency, can be found at our website: www.elsevier.com/permissions.

      This book and the individual contributions contained in it are protected under copyright by the Publisher (other than as may be noted herein).

      Notices

      Knowledge and best practice in this field are constantly changing. As new research and experience broaden our understanding, changes in research methods, professional practices, or medical treatment may become necessary.

      Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any information, methods, compounds, or experiments described herein. In using such information or methods they should be mindful of their own safety and the safety of others, including parties for whom they have a professional responsibility.

      To the fullest extent of the law, neither the Publisher nor the authors, contributors, or editors, assume any liability for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions, or ideas contained in the material herein.

      Library of Congress Cataloging-in-Publication Data

      A catalog record for this book is available from the Library of Congress

      British Library Cataloguing-in-Publication Data

      A catalogue record for this book is available from the British Library

      ISBN: 978-0-12-810420-0

      For information on all Academic Press publications visit our website at https://www.elsevier.com/books-and-journals

      Publisher: Sara Tenney

      Acquisitions Editor: Linda Versteeg-Buschman

      Editorial Project Manager: Tracy Tufaga

      Production Project Manager: Mohanambal Natarajan

      Designer: Matthew Limbert

      Typeset by TNQ Books and Journals

      List of Contributors

      Atul Agarwal,     Achillion Pharmaceuticals, Inc., New Haven, CT, United States

      John P. Atkinson,     Washington University School of Medicine, St. Louis, MO, United States

      Paul N. Barlow,     University of Edinburgh, Edinburgh, United Kingdom

      Scott R. Barnum,     University of Alabama at Birmingham, Birmingham, AL, United States

      Saverio Bettuzzi,     University of Parma, Parma, Italy

      Anna M. Blom,     Lund University, Malmö, Sweden

      Susan A. Boackle,     University of Colorado School of Medicine, Aurora, CO, United States

      Suzanne Bohlson,     Des Moines University, Des Moines, IA, United States

      Daniel C. Bullard,     University of Alabama at Birmingham, Birmingham, AL, United States

      David M. Cauvi,     University of California, San Diego, La Jolla, CA, United States

      Maciej Cedzyński,     Polish Academy of Sciences, Lodz, Poland

      Joseph M. Christy,     The Scripps Research Institute, La Jolla, CA, United States

      Liam G. Coulthard

      Royal Brisbane and Women’s Hospital, Herston, QLD, Australia

      University of Queensland, Herston, QLD, Australia

      Richard G. DiScipio

      Torrey Pines Institute for Molecular Studies, San Diego, CA, United States

      Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, United States

      Christian Drouet,     Université Grenoble Alpes, Grenoble, France

      Viviana P. Ferreira,     University of Toledo, Toledo, OH, United States

      Zvi Fishelson,     Tel Aviv University, Tel Aviv, Israel

      Christine Gaboriaud,     Institut de Biologie Structurale (IBS), Univ. Grenoble Alpes, CEA, CNRS, Grenoble, France

      Arije Ghannam,     Université Grenoble Alpes, Grenoble, France

      Berhane Ghebrehiwet,     Stony Brook University School of Medicine, Stony Brook, NY, Uniter States

      Ionita Ghiran,     Beth Israel Deaconess Medical Center, Boston, MA, United States

      Owen ​A. Hawksworth

      University of Queensland, Herston, QLD, Australia

      University of Queensland, St. Lucia, QLD, Australia

      Mingjun Huang,     Achillion Pharmaceuticals, Inc., New Haven, CT, United States

      David E. Isenman,     University of Toronto, Toronto, ON, Canada

      Jens C. Jensenius,     Aarhus University, Aarhus, Denmark

      Claudia Kemper,     King’s College London, London, United Kingdom

      David C. Kilpatrick,     Scottish National Blood Transfusion Service, Edinburgh, Scotland, United Kingdom

      Jennifer Laskowski,     University of Colorado School of Medicine, Aurora, CO, United States

      M. Kathryn Liszewski,     Washington University School of Medicine, St. Louis, MO, United States

      Kartik Manne,     University of Alabama at Birmingham, Birmingham, AL, United States

      Misao Matsushita,     Tokai University, Hiratsuka, Japan

      Paul Morgan,     Cardiff University, Cardiff, United Kingdom

      Valeria Naponelli,     University of Parma, Parma, Italy

      Sthanam V.L. Narayana,     University of Alabama at Birmingham, Birmingham, AL, United States

      Anne Nicholson-Weller,     Beth Israel Deaconess Medical Center, Boston, MA, United States

      Katsuki Ohtani,     Asahikawa Medical University, Asahikawa, Japan

      Marcin Okrój,     Medical University of Gdańsk, Gdańsk, Poland

      Luz D. Orozco,     Genentech Inc., South San Francisco, CA, United States

      Michael K. Pangburn,     The University of Texas Health Science Center at Tyler, Tyler, TX, United States

      Ramus Pihl,     Aarhus University, Aarhus, Denmark

      Steven D. Podos,     Achillion Pharmaceuticals, Inc., New Haven, CT, United States

      Kenneth M. Pollard,     The Scripps Research Institute, La Jolla, CA, United States

      Denise Ponard,     Université Grenoble Alpes, Grenoble, France

      Kristian Riesbeck,     Lund University, Malmö, Sweden

      Véronique Rossi,     Institut de Biologie Structurale (IBS), Univ. Grenoble Alpes, CEA, CNRS, Grenoble, France

      Theresa N. Schein,     University of Alabama at Birmingham, Birmingham, AL, United States

      Yu-Ching Su,     Lund University, Malmö, Sweden

      Anna S. Świerzko,     Polish Academy of Sciences, Lodz, Poland

      Nicole M. Thielens,     Institut de Biologie Structurale (IBS), Univ. Grenoble Alpes, CEA, CNRS, Grenoble, France

      Steffen Thiel,     Aarhus University, Aarhus, Denmark

      Joshua M. Thurman,     University of Colorado School of Medicine, Aurora, CO, United States

      Christopher B. Toomey,     University of California, San Diego, La Jolla, CA, United States

      Menno van Lookeren Campagne,     Genentech Inc., South San Francisco, CA, United States

      Nobutaka Wakamiya,     Asahikawa Medical University, Asahikawa, Japan

      Rick A. Wetsel,     The University of Texas Health Science Center at Houston, Houston, TX, United States

      Trent ​M. Woodruff

      University of Queensland, Herston, QLD, Australia

      University of Queensland, St. Lucia, QLD, Australia

      Preface

      The editors wish to thank all those who contributed entries for the second edition of The Complement FactsBook. We are especially appreciative of those authors who contributed two or three chapters including Drs. Paul Barlow, Dan Bullard, Richard DiScipio, Paul Morgan, Nicole Thielens, Christine Gaboriaud, Rasmus Phil, Jens Christian Jensenius, Steffen Thielens, Anna Blom, Liam Coulthard, Owen Hawksworth and Trent Woodruff. A special acknowledgement goes to Dr. Narayana Sthanam and Kartik Manne (UAB, Departments of Optometry and Biochemistry and Molecular Genetics) who generated the crystal structures used throughout the book. We also thank Drs. Doryen Bubeck and Marina Serna (Imperial College London, Department of Life Sciences) for providing the spectacular cover art images of the membrane attack complex. A special thanks goes to Donny Bliss who animated the activation of the complement pathways. This animation brings to life a complex set of pathways and makes complement more accessible to those in and out of the field.

      The editors would also like to thank the Elsevier publishing team, especially Linda Versteeg-Buschman, Halima Williams and Tracy Tufuga for their support, guidance and patience throughout the preparation of this text.

      Chapter 1

      Introduction

      Scott R. Barnum, and Theresa N. Schein     University of Alabama at Birmingham, Birmingham, AL, United States

      Abstract

      The aim of this book is to present biochemical, functional and relevant biological information about the proteins of the complement system. This edition of The Complement FactsBook contains updated information for all sections of the chapters in the first edition, particularly with respect to the structural domains and, where available, the crystal structure of the proteins. In addition, this edition covers information on complement mutant mice including their generation and disease phenotypes. Since the publication of the first edition of this book, many new complement proteins have been characterised and these proteins are now included in this edition.

      Keywords

      cDNA sequence; Chromosomal location; Deficiency; Function; Genomic structure; Human protein sequence; Mutant animals; Physicochemical properties; Polymorphic variants; Regulation of expression; Structure; Tissue distribution

      Aims and Scope of the Book

      The aim of this book is to present biochemical, functional and relevant biological information about the proteins of the complement system. This edition of The Complement FactsBook contains updated information for all sections of most chapters in the first edition, particularly with respect to the structural domains and, where available, the crystal structure of the proteins. In addition, this edition covers information on complement mutant mice including their generation and disease phenotypes. Since the publication of the first edition of this book, many new complement proteins have been characterised and these proteins are now included in this edition.

      As with the first edition, the focus of the book is on the human system, although accession numbers have been included for other species, particularly mouse and rat. In contrast to the first edition, the book is organised around functional families, namely the collectins, serine proteases, the C3 family, regulatory proteins and the anaphylatoxin and leukocyte receptors. The various protein modules that compose complement proteins are also highlighted, but their overlapping use between families makes them less useful as an organisational tool.

      Organisation of the Data

      Entries are subdivided into the following sections described below.

      Other Names

      Entries are identified by the recently established complement nomenclature.¹ This section also lists additional names used over the years for many of the proteins that may have been classified as members of other protein families (e.g., CR3, Mac-1; now known as CD18/CD11b) and for those characterised many decades ago when protein nomenclature was frequently based on electrophoretic mobility and other physicochemical features.

      Physicochemical Properties

      This section includes information on the number of amino acids in the mature protein and the leader peptide (if present), the pI, the molecular weight (predicted based on amino acid sequence and observed under reducing and nonreducing conditions where the data are available), the number and location of putative N-glycosylation sites, and if known whether the sites are occupied, the number and location of phosphorylation and tyrosination sites and the number and location of interchain disulfide bonds.

      Structure

      Details of the three-dimensional structure along with other unique structural features for the protein are described. For each protein a figure depicting the protein motifs is shown and, where available, a partial or complete crystal structure is provided. A key for the protein motifs is provided in Table 1.1 along with the complete names and abbreviations used throughout the book. Proteins such as CD59, which do not have a well-defined modular structure, are not included in the table.

      Function

      The mechanism of activation, the role of the protein and its biologically active fragments in the complement system are described in this section. Additional functions of the protein outside the complement system may also be described.

      Degradation Pathway

      Where appropriate a description and/or diagram of the degradation of the protein during the course of complement activation is provided. This is especially relevant for C3 and C4, which undergo extensive proteolytic degradation on complement activation.

      Tissue Distribution

      For secreted proteins, the known serum concentration is provided. In some cases, the plasma concentration is listed if there are known differences from that of the serum level. The levels in other biological fluids (cerebrospinal fluid, urine, tears, etc.) are also provided if known. The primary and secondary sites of synthesis are listed, but may not reflect the full repertoire of cells capable of synthesising a given protein. For membrane-bound proteins, the cell types clearly shown to express the protein are listed.

      Table 1.1

      Definitions of Protein Domain Diagrams Used Throughout This Book

      Regulation of Expression

      This section details the mechanisms that alter baseline synthesis of the proteins, whether or not the protein is an acute phase reactant and, disease-specific changes in expression.

      Human Protein Sequence

      Sequence is shown in single-letter amino acid code. Numbering starts with the initiator methionine residue. The leader sequence is underlined, as are cleavage sites between chains. Putative and known N-linked glycosylation sites are denoted by N. Additional specialised notations, such as unique posttranslation modifications, are described on a protein-by-protein basis.

      Protein Modules

      For the protein modules given in Table 1.1, the leader sequence, amino acid boundaries and exons are listed. Special structures such as the thioester bonds in C3 and C4 and the catalytic triad residues in the serine proteases are also listed.

      Chromosomal Location

      The chromosomal location in human, mouse and other species is provided. Closely linked genes are indicated.

      cDNA Sequence

      The cDNA sequence is shown. Where known, the sequence starts with the 5’ end of the message, otherwise the most 5’ sequence is given. Stop codons and polyadenylation signals where known are shown. All possible exons are included and exon–intron boundaries are denoted by underlining the first five nucleotides in each exon. Alternative splicing of exons is noted. No intron sequences are included. Discrepancies between published sequences are noted.

      Genomic Structure

      For each protein the structure of the gene is provided drawn to scale. The gene is represented as a single horizontal line and vertical lines indicate the positions of exons. In some cases unique genetic elements and their position within the gene are denoted.

      Accession Numbers

      Accession numbers from various databases are provided for human, mouse and other available species (where space permitted).

      Deficiency

      The mode of inheritance of deficiency in humans, as well as the phenotypic outcome of the deficiency, is described. Clinical syndromes associated with deficiencies are listed. The molecular basis of the deficiency is denoted as follows:

      C123 to G, S480 to L; two chromosomes/patients/families, where C is the normal nucleotide; 123 is the position in the presented nucleotide cDNA sequence; G is the mutant nucleotide; S is the normal amino acid; 480 is the position of the presented amino acid sequence; L is the mutant, non- or aberrantly functional amino acid; and two chromosomes/patients/families represents the number of times this mutation has been described.

      Polymorphic Variants

      Polymorphic variants at the protein or single nucleotide level are listed. In some cases the functional or structural consequences of the variation are described.

      Mutant Animals

      This is a new feature of The Complement FactsBook. Where mutant or transgenic mice have been generated, the following information is included: a description of the targeting construct, the targeting approach, genotype of injected eggs and crosses into different genetic backgrounds (if performed), phenotype in routine husbandry, phenotype in infectious disease and autoimmune models (if performed) and commercial availability (JAX labs and others).

      Reference

      1. Kemper C, Pangburn M.K, Fishelson Z. Complement nomenclature 2014. Mol Immunol. 2014;61:56–58.

      Chapter 2

      The Complement System

      Scott R. Barnum, and Theresa N. Schein     University of Alabama at Birmingham, Birmingham, AL, United States

      Abstract

      In this chapter, we introduce the complement system, the three main activation pathways and the terminal pathway, as well as discuss the history of complement discovery.

      Keywords

      Alternative pathway; Classical pathway; Complement; Lectin pathway; MBL pathway; Terminal pathway

      Historical Perspective

      Complement has been known by many names over the decades including alexin, cytase, addiment and opsonin of normal serum and its activity was divided into midpiece and endpiece.¹ Since the studies from the late 1880s and early 1900s, we now appreciate that complement comprises several activation pathways and mediates a plethora of biological activities including host defence, synaptic pruning and modulation of metabolism (Fig. 2.1).² The history of complement is complex. It is intertwined with the earliest studies of innate and adaptive immunity, infectious disease and the first vaccines. Space limitations preclude a detailed presentation of complement history in this text, so a series of bullet-point highlights are shown below. For a more detailed history the reader is referred to an excellent review and the references therein¹ and earlier perspectives by Pillemer³ and Lachmann.⁴,⁵

      Figure 2.1  Schematic of the complement pathways and some of the biological activities mediated by the complement.

      Modular Structure of the Components

      Sequencing of the complement proteins started in the early 1980s, and it quickly became apparent the proteins were comprised of multiple structural domains.⁶ In the first edition of this book, complement proteins were classified into functional groups based on these motifs. Since then several additional complement proteins have been identified and characterised, adding more motifs and complexity. The significant sharing of protein motifs across the functional families makes structural motif classification less valuable. Therefore, we have divided the proteins into five groups based on their overall functions within the complement system to allow for inclusion of all proteins rather than the older classification style based on structural motifs.

      The Collectins

      For the purposes of this edition, the collectins group will be limited to C1q, mannose-binding protein (MBL) and the ficolins/collectins. Although there are other structurally related family members, such as the surfactant proteins A and D, conglutinin and the C1q domain family members,⁷,⁸ their contribution to complement activity is minimal. The members of this family are readily identified by their dominant structural features: collagen stalks and C-terminal globular domains (Fig. 2.2). The globular domains interact with the Fc region of IgM and IgG antibodies in the case of C1q and carbohydrate moieties in the case of MBL and ficolins/collectins. All these proteins are composed of multiple polypeptide chains that are disulfide-linked in the collagen stalk region (the N-terminal portion), while the rest of the polypeptide chains form the globular domains.⁹–¹³

      Serine Proteases

      All the enzymes of the complement system are serine proteases of the trypsin subfamily and chymotrypsin family. Each enzyme has a serine protease domain with the classic catalytic triad of histidine, aspartic acid and serine (Fig. 2.3). Unlike most other serine proteases, the complement enzymes have a more restricted substrate specificity and generally slower enzyme kinetics.¹⁴–¹⁶ The remaining domains in these proteins are important for interaction with the collectins, each other (C1r/C1s and MASP1/2) or other components in the convertases (C2, Factors B and I).

      C3 Family

      The C3 family of proteins, C3, C4 and C5, is thought to have evolved from a common ancestral gene. The members share a modest homology within a given species (∼25%), but share higher homology for the same protein between different species.¹⁷ All three proteins are synthesised as a single-chain molecule, but undergo posttranslational modification including glycosylation, sulphation (C4), and cleavage to two (C3 and C5) or three (C4) polypeptide chains at conserved linker regions¹⁸−²⁰ (Fig. 2.4). The most important feature of these molecules is the presence of an internal thioester bond in C3 and C4.²¹,²² This chemical moiety is formed between cysteine and glutamic acid residues found in the α-chain of both proteins (Fig. 2.5). When C3 and C4 are cleaved on activation of the complement, the thioester bond becomes reactive allowing C3b and C4b to covalently attach to proteins or carbohydrates on the surface of pathogens, or host tissues, in the immediate vicinity.

      Figure 2.2  Modular structure of the collectins. See Table 1.1 for the key to the domains.

      Figure 2.3  Modular structure of the serine proteases. See Table 1.1 for the key to the domains.

      Terminal Pathway

      The terminal pathway is composed of the proteins C6 through C9, all of which share significant modular similarity (Fig. 2.6). The most important domain is the so-called membrane attack complex/perforin-like domain (MAC/PF) required for the formation of the MAC. These proteins are members of the MACPF/cholesterol-dependent cytolysins family of pore-forming toxins that undergo conformational changes and insert into lipid bilayers.²³,²⁴ These proteins are structurally similar to perforin, a molecule released by cytotoxic T cells to lyse target cells. The MAC forms by the association of C5b, C6, C7, C8 and multiple C9 molecules to form a pore of varying size based on the number of C9 molecules that insert into the complex. C9 can also polymerise under certain conditions in the absence of the C6–C8 complex.²⁵

      Figure 2.4  Modular structure of the C3 family of proteins. See Table 1.1 for the key to the domains.

      Figure 2.5  Schematic of the intact, metastable and transacylated thioester bond.

      Figure 2.6  Modular structure of the terminal pathway proteins. See Table 1.1 for the key to the domains.

      Regulatory Proteins

      Proteins that regulate the activation and functions of complement comprise a diverse group, but many are members of the so-called regulators of complement activation or RCA.²⁶ The RCA proteins are composed exclusively or almost exclusively of the complement control protein domain (CCP), also known as a short consensus repeat, or a sushi domain (Fig. 2.7A). This domain is approximately 60 amino acids in size with four conserved cysteine residues in which the first and third and second and fourth residues are cross-linked. The number of CCPs ranges from two in C2 and Factor B to as many as 37 in one of the CR1 alleles. A new addition to the RCA family since that last edition is the Factor H-related family of proteins.²⁷ A structural exception to the RCA proteins is CRIg, the only complement regulatory protein composed of immunoglobulin domains.²⁸,²⁹ All the RCA proteins bind proteolytic fragments of C3 and C4 and either serve as cofactors in their degradation or inhibit their biological activities.³⁰ The majority of these regulators are membrane-bound but some are found in plasma.

      A small subset of the regulators (Fig. 2.7B) serve to inhibit the formation of the MAC either on cell surfaces or in the fluid phase and share no structural homology (CD59, clusterin, vitronectin).³¹ C1-inhibitor (C1-INH) blocks the activity of the classical and lectin pathways by binding to the serine proteases that initiate activation of these two pathways.³² The last member of this group, properdin, serves to stabilise the C3 convertase of the alternative pathway, thus perpetuating C3b and C3 convertase generation through this pathway.³³ Properdin is important in the so-called amplification loop of the alternative complement pathway.

      Figure 2.7  Modular structure of the complement regulatory proteins. See Table 1.1 for the key to the domains. (A) The RCA family members are composed almost exclusively of complement control protein domains with the exception of CSMD1, which has a large number of CUB (complement C1r/C1s, Ugf, Bmp1) domains. These proteins exert their regulatory activity primarily on C3 and C4. (B) The remaining regulatory proteins, comprised of a mix of protein domains, control complement activity at multiple levels in the pathways.

      Figure 2.8  Modular structure of the leucocyte receptors. See Table 1.1 for the key to the domains.

      The Leucocyte Receptors

      The proteins in this group are expressed predominantly on leucocytes including T and B cells, dendritic cells and myeloid cells (Fig. 2.8). The exception is the expression of the anaphylatoxin receptors, which have been found on nearly every cell type examined with the exception of RBCs.³⁴,³⁵ As a group these receptors mediate many of the host defence functions of the complement that includes activation and chemoattraction of lymphocytes and myeloid cells, phagocytosis and induction of inflammation and the acute phase response.³⁵–³⁷ CR2 is traditionally grouped with the RCA proteins based on its chromosomal location in the RCA locus and its CCP domain composition. However, CR2 does not inhibit

      Enjoying the preview?
      Page 1 of 1