Which one of the following amino acid residues will destabilize an α-helix when inserted in the middle of the helix?

Q. Which one of the following amino acid residues will destabilize an α-helix when inserted in the middle of the helix?

(A) Pro

(B) Val

(C) Ile

(D) Leu

Ans: Pro

Solution:

(A) Pro

Proline (Pro) is the amino acid residue that will destabilize an α-helix when inserted in the middle of the helix.

The α-helix is a common secondary structure in proteins, characterized by a right-handed helical coil stabilized by hydrogen bonds between the backbone amide hydrogen and carbonyl oxygen of the peptide bonds. In an α-helix, the backbone forms a repeating pattern with a rise of 1.5 Å per residue and a 3.6 amino acids per turn.

Proline is unique among the standard 20 amino acids because its side chain forms a covalent bond with the amino group of its own backbone, creating a rigid cyclic structure. This conformational constraint prevents Proline from easily fitting into the regular hydrogen bonding pattern of an α-helix. When Proline is inserted in the middle of an α-helix, it disrupts the regular hydrogen bonding, leading to a kink or distortion in the helix. This destabilizing effect makes Proline a helix breaker and is why it is rarely found in the middle of α-helices.