Structure and Functions of Proteins

What Are Proteins?

1. Amino Acids — The Building Blocks

• A central α-carbon
• An amino group (–NH₂)
• A carboxyl group (–COOH)
• A hydrogen atom
• A unique side chain (R group) that gives each amino acid its identity

All amino acids in human proteins are L-α-amino acids (except glycine, which is neither D nor L because its α-carbon has two identical hydrogen substituents).

2. The Four Levels of Protein Structure

🔵 Primary Structure

Primary structure determines all higher levels of structure.

🔵 Secondary Structure

Key concept: The peptide bond has partial double-bond character — it is rigid and planar. Only the φ (phi) and ψ (psi) angles around the α-carbon can rotate. Allowed combinations of φ and ψ are plotted on a Ramachandran plot, which predicts permissible secondary structures.

🔵 Tertiary Structure

Domains: Large proteins can fold into independent structural units called domains. Each domain folds independently and may carry out a specific function.

🔵 Quaternary Structure

• Quaternary assembly allows cooperative O₂ binding (the binding of one O₂ facilitates the next)
• Forms binding sites for complex molecules (e.g., antigen binding by immunoglobulins)
• Increases protein stability

Not all proteins have quaternary structure. Myoglobin (single chain) has no quaternary structure; hemoglobin does.

3. Protein Folding and Denaturation

Folding

• The primary structure dictates the final 3D conformation (the "native conformation")
• Newly synthesized polypeptides are assisted by chaperones (chaperonins) — proteins that prevent premature misfolding and guide the chain to its correct shape
• Protein disulfide isomerase helps form correct disulfide bonds
• Peptidylproline cis-trans isomerase catalyzes isomerization of proline peptide bonds

Denaturation

• Heat, strong acids/bases, urea, detergents, and organic solvents disrupt non-covalent forces
• The protein loses its native conformation and becomes non-functional
• Denaturation is often irreversible
• Example: cooking an egg white (albumin)

Misfolding and Disease (Important for Clinical Context!)

4. Classification of Proteins

By Shape

By Composition

By Function (most important for MBBS!)

5. Ligand Binding

• Association constant (Kₐ) — higher Kₐ = tighter binding
• Dissociation constant (Kd) — lower Kd = tighter binding; Kₐ = 1/Kd

Quick Summary Table

Clinical High-Yield Points for 1st Year

1. Sickle cell anemia — Primary structure change (Glu→Val) → abnormal secondary/tertiary structure → HbS polymerizes → sickling
2. Scurvy — Deficiency of Vitamin C impairs hydroxylation of proline in collagen → defective collagen tertiary structure → connective tissue failure
3. Prion diseases — Abnormal tertiary structure propagates → neurodegenerative disease
4. Denaturation of proteins — Basis of sterilization (heat kills bacteria by denaturing their proteins)
5. Enzymes — Catalytic activity depends entirely on tertiary structure; denaturation = loss of enzyme activity