Question

An alpha helix of a protein is most likely to be disrupted if a missense mutation introduces the following amino acid within the alpha helical structure:

• A. Alanine.
• B. Aspartic acid.
• C. Tyrosine.
• D. Glycine.

Hint:

Glycine's tiny side chain gives the backbone extra flexibility, breaking the fixed geometry of an alpha helix.

Answer 1

The Correct Option is D

An alpha helix needs a backbone that can hold a steady, repeating twist, stabilized by hydrogen bonds every fourth residue. Some amino acids fit this shape easily, others fight against it. Let's check each option.

1. Alanine: Its side chain is just a methyl group, small and simple. This lets the backbone sit comfortably in the helical twist, alanine is in fact one of the strongest helix formers, so putting it into a helix would not disrupt it.
2. Aspartic acid: This side chain carries a negative charge at physiological pH. It can fit within a helix without much trouble, though several charged residues of the same sign placed close together can create some repulsion. On its own it is not a classic helix disrupter.
3. Tyrosine: A bulky ring-shaped side chain, it can add some steric bulk but tyrosine residues are regularly found inside natural alpha helices, so it is tolerated reasonably well.
4. Glycine: Its side chain is only a single hydrogen atom, giving the backbone extra freedom to rotate that other residues do not have. This flexibility works against the fixed, repeating angles an alpha helix depends on, so glycine is the classic helix breaker.

Between the four, only glycine's lack of a real side chain gives the backbone enough extra freedom to break the strict geometry of the helix.

Let's summarize:

• Alpha helices need a backbone locked into regular phi and psi angles.
• Glycine's tiny side chain gives too much backbone freedom, making it a helix breaker along with proline.

So a missense mutation that introduces glycine into a helical region is the one most likely to disrupt that alpha helix.