An Overview of Protein Functions

Proteins are Made of Amino Acids

20 amino acids

9 ESSENTIAL AMINO ACIDS IN HUMANS

phenylalanine, valine, threonine, tryptophan, isoleucine, methionine, leucine, lysine and histidine
 How to build a Protein
Polymerization reactions do not happen spontaneously. The process increases organization
while decreasing entropy. It requires energy input to take place.

H H O H O H H
O O
H2N C C + H2N C C H2N C C N C C + H2O
OH Amino OH OH
H CH3 H Peptide CH3
Carboxyl group bond
group

N-terminus C-terminus
H H O H H O H H O H H O H H O H H O H H O H H O
H N C C N C C N C C N C C N C C N C C N C C N C C OH

H CH3 CH2 CH2 CH2 CH CH2 CH2

OH C OH H3C CH3 SH
O
OH
N-terminus C-terminus

H2N Gly Ala Ser Asp Phe Val Tyr Cys COOH
1 2 3 4 5 6 7 8
 Protein Folding
 The function of a protein depends on its three-dimensional structure and on its ability
change shape and back.

 The three-dimensional structure of a protein is determined by the order of amino acid in the
protein chain as well as by the interaction of the protein with other molecules.

 Most proteins, given a particular sequence can fold in more than one way. The correct folding
is achieved inside the cell with the help of a family of proteins called chaperones.

 Changes in sequence MAY change 3D structure

 Depends on the particular substitution

 Protein folding is a stepwise process. Therefore the final conformation is determined by up

to four levels of structures
 Primary
 Secondary
 Tertiary
 Quaternary (only some proteins)
he secondary structure of a protein; alpha helices and beta shee
The Sequence of Amino Acids Determines the Shape of
the Protein Because of Side Chains Interactions
Some proteins have a quaternary structure.
The quaternary structure is determined by the association of more than one polypeptide
chain
This association depends on the protein sequence because it is held by interactions
between side chains.
Size and Shapes of Some Proteins
Beta Galactosidase
 Proteins: Structure-Function Relationship

 Function related to three-dimensional structure.

Enzyme/Substrate, Antigen/Antibody interactions based on
complementary patches on their surface
 Shape

 Proteins can do so many different tasks because they

come in so many shapes

 Proteins can do so many different tasks because they can

change shape

 Shape allows proteins to be very specific

 How to Change a Protein’s Shape
 Protein/protein interactions
 Because the three-dimensional structure is determined by
chemical bonds between amino acids, interactions with
other proteins can alter these relationships and change the
shape.
http://blausen.com/en/video/me
mbrane-protein-binding-of-hiv-
and-a-t-cell/
Changing Shape: Prion Disease
Changing Shape: Prion Disease
How to Change a Protein’s Shape
 Phosporilation.
 Because the three-dimensional structure is determined by
chemical bonds between amino acids, interactions with
negatively charged phosphate groups can alter these
relationships and change the shape.
Changing Shape: Phosphorilation
 How to Change a Protein’s Shape
 Protein/protein interactions (Think enzymes)

 Phosporilation (Think kinesin)

Protein kinases Protein

are enzymes phosphatases
that ADD are enzymes
phosphate that REMOVE
groups to phosphate
proteins groups to
proteins

Phosphorylation changes a protein shape (phosphate groups negatively charged)

Changing shape changes activity/Used by the cell to turn ON/OFF the activity of specific
proteins
 Mutations
 Mutations are changes in the DNA sequence.

 Mutations can be defined as point mutations, affecting only one

or a few bases

 Or can involve large segments of DNA

 Or even entire chromosomes

 For now, we will discuss only point mutations

Causes of DNA mutations
 DNA Repair

 Mutations are a fact of life. They happen.

Very imprtant as a source of genetic variation

But, they can have very deleterious effects

Cells employ a variety of mechanisms to repair

mutations
 DNA repair Mechanisms. 1
DNA polymerase proofreading activity. During DNA replication
 DNA repair Mechanisms. 2
Excision-Repair. Protects against external insults during the life of
the cell
 Consequences of Point
Mutations
 Prevent a protein from being synthesized

 Change the shape/function of a protein

 The way a protein interacts with other molecules

Cystitc Fibrosis
 DNA point mutation can lead to a different
amino acid sequence.

Start of coding sequence Phenotype

DNA CAC GTG GAC TGA GGA CTC CTC
sequence GTG CAC CTG ACT CCT GAG GAG

Amino acid Normal

sequence
Histidine Threonine Glutamic
Valine Leucine Proline Glutamic
acid Normal red blood cells
acid
CAC GTG GAC TGA GGA CAC CTC
DNA
GTG CAC CTG ACT CCT GTG GAG
sequence

Amino acid
sequence Mutant

Histidine Threonine Glutamic

Valine Leucine Proline Valine acid Sickled red blood cells
 Sickle Cell Hemoglobin
Mutation chanages the way individual hemoglobin
molecules interact with each other
Sickle Hemoglobin
Changing Proteins Interactions:
Sickle Cell Disease
Sickle Cell Disease Genetics
 Selection Against Lethal
Recessive Alleles

Fast first, then very slow. Does not get eliminated because protected in heterozygous.
Sickle Hemoglobin Frequencies

o 1/500 African Americans have Sickle Cell

Disease
o 1/12 African Americans are carriers for
Sickle Cell
o Less than 1 in 100,000 are carriers in the
rest of the population!
Sickle Hemoglobin Frequencies

In the United States, about 1 in 500 African-Americans

develops sickle cell anemia.
In Africa, about 1 in 100 individuals develops the disease.
Why is the frequency of a potentially fatal disease so much
higher in Africa?
Infectious diseases have affected our evolution. Sickle cell
disease is a good example.
Figure 23.10 Mapping malaria and the sickle-cell allele
Why Sickle Cell Allele Protects

 Plasmodium parasite cannot digest mutant

hemoglobin
 Plasmodium causes affected cells to sickle
and die before the parasite can reproduce
 Malaria

 Caused by the protozoa parasite of the Genus Plasmodium

 P. falciparum
 Deadliest
 P. vivax
 Mild
 P. ovale
 Rare, mild
Sexual stage
 P. malariae
 Rare, mild

 Transmitted by female mosquitoes of the Genus Anopheles

 350 species known. Only 60 carry malaria
Malaria Burden
Distribution of P. falciparum (blue)
and P. vivax (yellow)
Distribution of Anopheles Species
 Mostly Affects Children

Maternal immunity worn off

NO acquired Immunity
 Treatment

Cloroquine
 Prevents hemoglobin digestion

Artemisin
 Reacts with heme group to produce
free radicals
Plasmodium falciparum Drug
Resistance
 Discovery of Penicillin
Alexander Fleming, 1929
Evolution of Antibiotic Resistance
Antibiotics
How Bacteria Become Resistant

5. Mutation on target protein

prevents antibiotic binding
VGT
(rifampicin)
 Antibiotic Resistance Study

 Frequency of resistant bacteria in a population (E. coli)

 Identify the mutation that makes them resistant