A lab studying collagen biosynthesis compared two procollagen variants: one contains a Gly→Val substitution within a (Gly-X-Y) repeat. Both variants are translated to full length, but the mutant shows increased intracellular degradation. Which statement best emphasizes the role of primary structure (peptide bond-linked sequence) in downstream stability without attributing the effect to disulfide bonds?
(Assume degradation occurs via ER-associated pathways.)
- The Gly→Val substitution increases peptide bond resonance, making the backbone unbreakable and therefore targeted for degradation.
- The Gly→Val substitution prevents peptide bond formation at that site, so translation stops and triggers degradation.
- The Gly→Val substitution removes a disulfide bond in the collagen triple helix, destabilizing the primary structure directly.
- The Gly→Val substitution changes the amino acid sequence while preserving peptide bond connectivity; altered sequence can impair proper folding/processing and increase degradation. (correct answer)
Explanation: This question assesses how primary structure mutations affect stability via folding, distinct from peptide bonds themselves. Peptide bonds link the sequence, with mutations altering residues but not connectivity. In these procollagen variants, Gly to Val increases degradation despite full length. The correct answer, A, follows because sequence change impairs folding, targeting degradation. A common distractor, like choice B, incorrectly posits synthesis stop, contradicting length data. In biosynthesis studies, link sequence to downstream fate. Avoid confusing with disulfide or resonance effects.