Protein Structure and Function: Study Notes

Chapter 3: Protein Structure and Function

Importance of Proteins

Proteins are essential macromolecules that perform a wide variety of functions in all living organisms. They make up more than 50% of the dry mass of most cells and are involved in nearly every cellular process.

• Structural: Provide support and shape to cells and tissues (e.g., keratin in hair and nails, flexibility in red blood cells).

• Transport: Move ions and molecules across cell membranes.

• Communication: Act as hormones or signaling molecules (e.g., glucagon signals the liver to release glucose).

• Movement: Enable muscle contraction (e.g., actin and myosin proteins).

• Defense: Function as antibodies and complement proteins in the immune system.

• Catalysis: Serve as enzymes, lowering the activation energy required for biochemical reactions.

Amino Acids (AA) – Building Blocks

Structure of Amino Acids

Amino acids are the monomers that make up proteins. Each amino acid has a central carbon atom (α-carbon) bonded to four different groups:

• Hydrogen atom (H)

• Amino group (–NH2): Ionizes to –NH3+ in water

• Carboxyl group (–COOH): Ionizes to –COO– in water

• R group (side chain): Determines the chemical properties and identity of the amino acid

Ionization of amino and carboxyl groups keeps amino acids soluble and reactive in aqueous environments.

Categories of Side Chains (R Groups)

The R group, or side chain, classifies amino acids into four main categories based on their chemical properties:

• Acidic: Side chains contain a carboxyl group and are negatively charged at physiological pH.

• Basic: Side chains contain an amino group and are positively charged at physiological pH.

• Uncharged Polar: Side chains contain electronegative atoms (such as O or N) and can form hydrogen bonds.

• Nonpolar (Hydrophobic): Side chains are mostly hydrocarbons (C–H), do not form hydrogen bonds, and tend to cluster away from water.

Polymers: From Amino Acids to Proteins

Protein Formation

Proteins are polymers composed of one or more polypeptide chains, each formed by linking amino acids through peptide bonds.

• Peptide Bond Formation:

  • Occurs via a condensation (dehydration) reaction, which releases water.

  • The carboxyl group of one amino acid bonds to the amino group of the next amino acid.

  • Equation: $\text{Amino Acid}_1 + \text{Amino Acid}_2 \rightarrow \text{Dipeptide} + H_2O$

• Peptide Backbone:

  • Has directionality: from the N-terminus (amino end) to the C-terminus (carboxyl end).

  • R groups project outward, which is important for protein folding and function.

  • Some rotation is possible around single bonds, allowing flexibility.

Levels of Protein Structure

Proteins have a hierarchical structure with four distinct levels, each contributing to the final shape and function of the protein.

1. Primary Structure (1°)

• The unique sequence of amino acids in a polypeptide chain, determined by the gene encoding the protein.

• This sequence dictates all higher levels of protein structure.

• Example: Sickle cell anemia is caused by a single amino acid substitution (valine for glutamate) in the hemoglobin protein.

2. Secondary Structure (2°)

• Local folding of the polypeptide chain, stabilized by hydrogen bonds between the backbone carbonyl (C=O) and amino (N–H) groups.

• Two common types:

  • α-helix: A coiled, spring-like structure.

  • β-pleated sheet: A folded, sheet-like structure stabilized by hydrogen bonds.

3. Tertiary Structure (3°)

• The overall three-dimensional shape of a single polypeptide chain, resulting from interactions among R groups (side chains).

• Types of interactions include:

  • Hydrophobic interactions: Nonpolar side chains cluster together away from water.

  • Ionic bonds: Form between acidic and basic side chains.

  • Van der Waals forces: Weak, temporary attractions between atoms.

  • Disulfide bridges: Covalent bonds between sulfur atoms in cysteine residues.

  • Hydrogen bonds: Between polar side chains.

4. Quaternary Structure (4°)

• Formed by the association of two or more polypeptide chains (subunits) into a functional protein complex.

• Example: Hemoglobin consists of four subunits (2α and 2β), each with an iron-containing heme group.

Protein Folding

Protein folding is a hierarchical process (primary → secondary → tertiary → quaternary) that is essential for proper protein function.

• Correct folding is crucial for biological activity.

• Misfolding leads to denaturation, which can be caused by changes in pH, salt concentration, or temperature. Denatured proteins lose their function.

• Folding can be regulated and is sometimes reversible (e.g., some proteins fold upon activation by Ca2+ signaling).

Special Topic: Prions

Prions are a unique class of infectious agents composed solely of misfolded proteins. They can induce normal proteins to adopt the misfolded, disease-causing conformation.

• Prions have the same amino acid sequence as normal proteins but an abnormal shape.

• They cause neurodegenerative diseases, such as mad cow disease (bovine spongiform encephalopathy, BSE).