Biochemistry Lecture 7

Q: What determines the folding of a polypeptide chain?

A: The amino acid sequence determines folding, starting with secondary structure formation.

Q: What role do breaker amino acids play in folding?

A: They interrupt secondary structure and create flexible turns or loops that allow folding.

Q: What are common breaker amino acids?

A: Gly, Pro, Ser, Asn, and Asp.

Q: What drives the clustering of nonpolar side chains?

A: Hydrophobic interactions forming the protein’s nonpolar core.

Q: What is the energy contribution of hydrophobic interactions to protein stability?

A: About 50% of the energy stabilizing the folded form.

Q: What are the main tertiary structure types?

A: α-helix clusters, antiparallel β-barrels, parallel α/β barrels, and parallel α/β sandwiches.

Q: Give examples of fibrous proteins.

A: α-keratin (α-helix), fibroin (β-sheet), collagen (triple helix).

Q: What gives proteins a globular shape?

A: Folding due to flexible turns and loops from breaker residues.

Q: What interactions stabilize the folded state? (5 types)

A: Hydrophobic interactions, van der Waals forces, ion pairs, hydrogen bonds, and disulfide bonds.

Q: What are van der Waals interactions?

A: Weak attractive forces between atoms at ideal contact distances (~0.1–1 kJ).

Q: Why is correct folding crucial for van der Waals interactions?

A: Only properly folded proteins achieve many optimal atom-to-atom contacts.

Q: What are supersecondary structures?

A: Simple combinations of secondary structures, e.g., helix-turn-helix, β-hairpins, βαβ units.

Q: What is a helix bundle?

A: A group of α-helices held by interlocking nonpolar residues and sometimes by ion or H-bond pairs.

Q: What sequence pattern favors α-helices with one nonpolar face?

A: -PNNPPNP- (polar/nonpolar alternation every ~3–4 residues).

Q: What structure results from mostly β-sheet-forming amino acids?

A: Antiparallel β-sheets or β-barrels.

Q: What is a Greek key motif?

A: A four-stranded antiparallel β-sheet formed from hairpin turns.

Q: Why are antiparallel β-sheets more stable than parallel ones?

A: Better H-bond alignment between strands.

Q: What sequence pattern favors β-strands?

A: Alternating polar and nonpolar amino acids. → Antiparallel

Q: What is a parallel α/β-barrel?

A: A cylindrical fold of parallel β-sheets with α-helices connecting strands.

Q: What is a parallel α/β sandwich?

A: A central β-sheet covered by α-helices on both sides (e.g., lactate dehydrogenase).

Q: What are protein domains?

A: Independent folding units (~10–20 kDa) that may differ within a single protein.

Q: Example of a multi-domain protein?

A: Lactate dehydrogenase — contains two α/β sandwich domains.