03 Proteins I An Introduction to Protein Structure and Function

Outline

3.1 Amino acid chemistry
3.2 Proteins are polymers of amino acids
3.3 Proteins are molecules of defined shape and structure
3.4 Examples of protein structures and functions

Learning Objectives

1. Compare the 20 amino acids commonly found in proteins with each other in terms of their chemical properties.
2. Describe the general properties of proteins and peptides.
3. Analyze the different levels of protein structure.
4. Describe several examples that illustrate the diversity of protein structures and functions.

Section 3.1 Learning Objective

Compare the 20 amino acids commonly found in proteins with each other in terms of their chemical properties.

Amino Acids

The building blocks of proteins
Contain amine and carboxylic acid functional groups
There are 20 amino acids, all with different side chains (residues).

Figure 3.2 Structure of an amino acid.

Alpha carbon and the side chain (R group)
There are 19 alpha amino acids (amino group, a central alpha carbon, and a carboxyl group) and 1 imino acid (proline – contains a secondary amine)

Amino Acids

The majority are achiral.
Figure 3.3 Chirality of amino acids.

NOTE: Nature prefers the L-enantiomer for amino acids

Zwitterion Defined

Zwitterion is a molecule that possesses both a positive and negative charge.

• An amino acid at neutral pH is an example.
  Figure 3.4 Zwitterionic nature of amino acids.
  
  Amino acids can have different charges at different pHs

Amino Acid Classification

Nonpolar (hydrophobic)—usually an alkyl group, an aromatic ring, hydrogen, or a nonpolar collection of atoms.
Polar—the side chain is polar or ionic.

• acidic—the side chain is a carboxylate ion.
• basic—the side chain is an amine.
• neutral—the side chain in an alcohol, thiol, or amide.
  Branched chain amino acids (BCAAs) = Valine, leucine and isoleucine.
  Polar acidic amino acids have negatively charged side sides, whereas lysine, arginine, and histidine have positively charged side chains

Amino Acid Structures

Figure 3.5 Amino acids.

Side Chain Ionization

Amino acid side chains play a pivotal role in protein folding and protein–protein interaction.
These side chains may become ionized at different pKa values.
This has an effect on overall protein structure.

The pKa Values of Amino Acid Side Chains

Roles of Amino Acids in Biochemistry

Amino acids serve a variety of roles in biochemistry including:

• lipid metabolism
• amino acid catabolism
• neurotransmission
  Figure 3.6 Amino acids not commonly found in proteins.
  

Section 3.2 Learning Objective

Describe the general properties of proteins and peptides.

Peptide Bond Defined

Peptide bond is the linage between two amino acids.

• This is an amide linkage between the carboxyl group of amino acid and the amino group of the next.
• A water molecule is removed in order for an amide bond to form.

Figure 3.7 Peptide bond.

Typically in a trans conformation to prevent steric hindrance

Peptides Defined

Peptides are linear polymers of amino acids.

• Dipeptides have two linked amino acids.
• Oligopeptides have 4–20 amino acids.
• Polypeptides contain 20 or more peptides linked together.
• Proteins tend to be greater than 100 amino acids.

Monomers versus Multimers

Monomers

• Single chains of amino acids folded into an active protein
  Multimers
• Consist of several subunits
• Subunits labeled based on function (i.e., catalytic and regulatory)

Cofactors Defined

Cofactors are nonprotein groups required for protein binding or activity.

• Can be divided into two categories: minerals (metal ions) and vitamins (small organic groups)
• Metal ions (Ca2+, Mg2+, Zn2+, Fe2+, and Cu2+)
• Organic groups (NAD+ and FAD, pyridoxal phosphate)
• The difference between apoproteins ( do not contain cofactor) and holoproteins (complete protein)

Examples of Cofactors

Figure 3.12 Examples of cofactors.

Amino Acid Modifications

Figure 3.13 Amino acid modifications.

Explain the difference between reversible (phosphorylation) and irreversible (ubiquitination) modifications.

Kinases Defined

Kinases are enzymes that catalyze phosphorylation reactions.

• ATP is typically the source of phosphate.
• Phosphates can add on to the hydroxyl groups of serine, threonine, or tyrosine.
• Phosphorylation can change the activity of an enzyme and is thought to act as a switch in the cell.

Section 3.3 Learning Objective

Analyze the different levels of protein structure.

Four Levels of Protein Structure

Primary
Secondary
Tertiary
Quaternary

Primary Structure

Linear arrangement of amino acids
The order of amino acids is crucial to its function.
Figure 3.14 Primary sequence of a protein.

Discuss how substitutions may affect the protein
Conservative substitution = substitutions of the same polarity may not affect function

Cystic Fibrosis: An Example of Mutation

Figure 3.16 Cystic fibrosis.

Secondary Structure

Held together by hydrogen bonding
Consists of two major structural elements:

• α helix
• β sheet
  Can also have turns and coils (loops)

Alpha Helix

Most common structure observed in proteins
Figure 3.17A Alpha helix.

Gly and Pro discourage helix formation

Beta Sheet

Can be parallel or antiparallel
Figure 3.18 Beta sheet.

Hairpin Loops and Turns

Figure 3.19 Turns and coils.

Tertiary Structure

Gives the overall shape of the protein
Figure 3.20 Tertiary structures.

Motifs versus Domains

Motifs

• Combinations of secondary structures
  Domains
• Pieces of a protein that retain their structure in the absence of the rest of the protein
• A discretely folding structure

Alpha Structures

Figure 3.21 Alpha structures.

Beta Motifs

Contain mostly β structures

• Include the β barrel, Greek key motif, and β propeller
  Figure 3.22 Beta structures.
  

Bonding Forces Involved in Tertiary Structure

Forces include

• hydrogen bonding
• London dispersion forces
• dipole–dipole interactions
• salt bridges
• cation–π interactions
• disulfide bonds
  Explain each type of bonding and point out strongest and weakest forces

Stabilizing Forces Involved in Protein Structure

Figure 3.23 Forces involved in stabilizing proteins.

Hydrophobic Effect Defined

Hydrophobic effect describes the phenomenon in which hydrophobic groups cluster together.
London dispersion and Van Der Waals forces

Quaternary Structure

Complex structure that incorporates multiple subunits or different proteins
Figure 3.24 Quaternary structure.

Section 3.4 Learning Objective

Describe several examples that illustrate the diversity of protein structures and functions.

Aquaporin: A Transmembrane Protein

A protein that acts as a pore in the membrane
Selectively allows water to pass in and out of the cell
Consists of six transmembrane α helices

Aquaporin

Figure 3.25 Aquaporin.

Chymotrypsin: An Enzyme

Produced by the pancreas and secreted into the intestinal lumen
Cleaves dietary protein into peptides
Composed of two β barrels and one short α helix
As an enzyme, contains an active site and regulatory site

Structure of Chymotrypsin

Figure 3.26 Chymotrypsin.

Collagen: A Structural Protein

A fibrous protein mostly concentrated in muscle and connective tissue
Composed of a “triple helix”
Contains glycine (33%), proline (16%), and hydroxyproline (16%)
Also called a collagen helix

Structure of Collagen

Figure 3.27 Collagen.

Hemoglobin: A Transport Protein

A globular, tetrameric protein found in red blood cells
Contains four subunits
Transports oxygen to the blood
Uses heme as a cofactor for each subunit
Composed of mostly α helices joined by turns

Hemoglobin Structure

Figure 3.28 Hemoglobin.

Immunoglobulins: Binding Proteins

Molecules of the immune system that recognize and bind to antigens
Act as adapter molecules between the foreign molecule (antigen) and the immune system cells required to neutralize it

Basic Structure of Immunoglobulins

Figure 3.29 Immunoglobulins.

Insulin: A Signaling Protein

A protein hormone produced by pancreatic β cells
A growth factor that signals cells to store energy and divert energy to growth
Interrupted or impaired signaling can result in diabetes
Discuss the difference between Type I (lack of insulin signal) and Type II (defect in insulin receptor) diabetes

Structure of Insulin

Figure 3.30 Insulin.

Myosin: A Molecular Motor Protein

Acts as a molecular motor in which energy is used to elicit a muscle contraction and transport vesicles in the cell
Contain heavy and light chains

• Heavy chain—interacts with the cytoskeletal protein, actin
• Light chain—plays a role in binding Ca2+
  Mechanism for myosin and movement with ATP

Myosin Structure

Figure 3.31 Myosin.