Give two reasons to explain why a proline residue in the middle of an alpha helix is predicted to destabilize the helical structure.
The correct answer and explanation is:
A proline residue in the middle of an alpha helix is predicted to destabilize the helical structure for two main reasons:
- Lack of Amide Hydrogen for Hydrogen Bonding
Proline has a unique structure compared to other amino acids. Its side chain forms a cyclic structure by bonding with the amine group, which restricts the ability of proline to participate in hydrogen bonding. In the alpha helix, the backbone amide groups of each amino acid form hydrogen bonds with the carbonyl groups of the amino acid located four residues earlier. These hydrogen bonds are critical for stabilizing the helical structure. However, the rigid cyclic nature of proline prevents it from forming this key hydrogen bond, disrupting the regular hydrogen bonding pattern needed to stabilize the helix. - Rigid, Fixed Structure of Proline
Proline has a rigid structure that introduces a kink or bend in the polypeptide chain. The ring structure of proline restricts the rotation around the C-N bond in the backbone, which is normally flexible in other amino acids. This rigidity creates a structural distortion in the helix, as it does not fit well with the ideal geometry of the alpha helix, where each residue should allow for smooth, continuous coiling. When proline is placed in the middle of an alpha helix, this kink disrupts the regular coiling and induces a bend in the helix, leading to destabilization.
Together, these factors contribute to the destabilization of the helical structure, making proline an unfavorable residue in the middle of alpha helices. While proline can be found at the helix’s end or in certain turns, its placement within the helix typically leads to a break in the structure or a loss of stability.