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Proteins
Carry out almost all cellular activities
Enzymes Structural elements

As many as 10,000 different proteins in mammalian cell

Each has unique structure Each has specific interactions with other molecules

Long continuous polymer of amino acids

Proteins
Exhibit a high degree of selectivity when interacting with other biological molecules
DNA cutting enzymes: recognize specific DNA sequence and cut the DNA molecule Transcription factors: recognize specific DNA sequences and bind to the DNA molecule

Amino Acids = Monomers

20 common amino acids Share common skeleton
Amino group g p Carboxyl group Single carbon separating groups

Each position in a DNA molecule can potentially be one of four nucleotides. The longer the DNA sequence, the greater the number of possible nucleotide combinations.
6 nucleotide motif = 4^6 or 4,096 possible unique sequences 7 nucleotide motif = 4^7 or 16,380 possible unique sequences 8 nucleotide motif = 4^8 or 65,536 possible unique sequences

Side chain attached to C

Designated R Basis for name of amino acid

Glycine: R = H All others: R = another group

4 different groups attached to C Can exist as stereoisomers D or L form

Amino acids linked by peptide bond

Bond between carboxyl group of 1 amino acid and amino group of next amino acid Water removed during formation

L form almost always used in proteins

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Peptide Chain
Individual amino acid = residue Amino (N) terminus = end of chain with free amino group Carboxyl C) terminus = end of chain with free carboxyl group b l

Peptide Chain
Backbone = common skeleton of residues Different properties conferred by side chains

Amino acids grouped by nature of side chain

Polar charged R groups

Polar uncharged

Hydrophilic Hydrophilic Relatively strong organic acids and bases Almost always ionized at physiological pH Histidine exception Able to form ionic bonds with other charged molecules Weakly acidic or basic Partial positive or negative charge physiologic pH Can form H bonds with other molecules including H2O

Nonpolar

Unique properties

Hydrophobic Usually lack O or N Differ in size and shape Can pack tightly into spaces in core of protein Interact through hydrophobic associations and van der Waals forces

Glycine
R=H Small and flexible Allows hinged movement of backbone Hydrophobic OR Hydrophillic

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Cysteine
Polar uncharged side chain containing sulfur Can form disulfide bond with S of another cysteine Covalent bond formed by oxidation reaction Cytoplasmic environment unfavorable for formation of disulfide bonds Important in stabilization of 3-D structure of extracellular proteins

Proline
Hydrophobic side chain Part of ring formed by N of amino group Causes kinks in polypeptide chain Disrupts ordered secondary structure

Post-Translational Modifications (PTMs)

Alterations to the side chains of the amino acids after their incorporation into a polypeptide chain PTMs can occur in the cytoplasm, golgi appartus, or endoplasmic reticulum Allow a single polypeptide to exist as a number of distinct biological molecules Three common forms of PTMs Phosphorylation Glycosylation Ubiquitination PTMs are specific to different amino acids

Phosphorylation
Serine, threonine, tyrosine Kinase: protein that adds a phosphate group using ATP as a source Phosphatase: p p protein that removes the phosphate group Activation or deactivation of a proteins function can be controlled by its phosphorylation state.

Glycosylation
Asparagine, serine, threonine Addition of one or more sugar monomers to the side chain Glycoproteins y p Affects a protein solubility, targeting, 3dimensional folding, half-life, interaction with other proteins.

Ubiquitination
Ubiquitin molecule added to the side group of lysine Renders target protein susceptible to degradation

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Facts about Proteins

Not all amino acids in every protein Different amounts of amino acids in proteins May contain additional amino acids
Formed by modification of amino acid after incorporation into polypeptide chain

Primary structure
Specific linear sequence of amino acids Information for sequence encoded in DNA Determines conformation
Proper conformation necessary for function p y

Defined and predictable structure based on

Nature of the amino acids in protein Order of amino acids Environment Ubiquitin: 76 amino acids
MQIFVKTLTGKTITLDVEASDTIENVKAKIQDKEGIPPDQQRLIFAGKQLEDGRT LSDYNIQKESTLHLVLRLRGG

Change in amino acid due to a point mutation Affect on structure depends on nature of side chain
May have little or no affect if side chain has similar properties More affect if side chain has different properties

Secondary Structure
2 regular structures often present 1. Helix
Linear chain of amino acids coiled into spiral helix Backbone of polypeptide on inside of helix Side chains oriented outward

Certain regions of p g protein more critical for function

Greater impact if change in 3-D structure or properties

Sickle Cell Anemia

Charged Nonpolar

Stabilized by H bonds between adjacent amino acids Can be stretched

2. -Pleated sheet
Formed regions of polypeptide chain lying side by side Pleated structure to each segment Oriented parallel or antiparallel

Other regions of polypeptide chain

Turns Loops Hinges Fingerlike projections
Sheet Helix

Stabilized by hydrogen bonds between strands perpendicular to polypeptide chains Highly extended structure

Often most flexible regions

Parallel

Antiparallel Connecting segment

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Tertiary Structure
Overall 3-D structure of polypeptide Depends in part on environment Stabilized by bonds and interactions
Hydrophobic regions Hydrophobic interactions Van der Waals forces Hydrophilic regions Hydrogen bonds Ionic bonds Covalent disulfide bonds between cysteines

Aqueous Environment

hydrophilic side chains

hydrophobic side chains

Domains
Distinct modules in polypeptide chain
Usually 50-350 amino acids Fold independently into stable structures

Usually 2 or more domains in larger proteins

Often act in semi-independent manner Usually perform different functions

Single domain in small proteins

Proteins grouped into families

Share similar amino acid sequence and conformation Superfamily = family with many members

Motifs within polypeptide

Recurring thematic element Defined arrangements of helices and/or strands coiled coil motif

Classes of Proteins Based on Overall Conformation

Fibrous
Extended proteins Form cables or sheets

Globular
Compact globular shape Included most enzymes / barrel motif

Combinations of these

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Quaternary Structure
Association of 2 or more polypeptide chains to form protein with single function
Each polypeptide chain = subunit Linked by disulfide and/or noncovalent bonds

Proteins may be linked together into multiprotein complexes

Different function for each protein in complex Functions often linked May be transient and dynamic association

Identical or nonidentical subunits

Homomeric- identical subunits Heteromeric- nonidentical subunits

homodimer

Combinations with other macromolecules

Glycoproteins Lipoproteins Nucleoproteins

heterotetramer

Correct folding critical for correct function

Can self-assemble into correct conformation
unfolded native state

Folding in cell
Often folds with aid of molecular chaperones
Helps prevent incorrect associations with other molecules in crowded environment

Translation: Protein Synthesis

Coiled Coil Motif

http://www.youtube.com/watch?v=Ikq9AcBcohA& feature=related

http://www.youtube.com/watch?v=S8ddylPOn5w &feature=related

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Zn finger Motif

Next Lecture
Bioenergetics
Chapter 3

http://www.youtube.com/watch?v=GRL_rdB30GY &feature=related

Pages 85-93