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

Step 1: Recall what holds an alpha helix together.
An alpha helix is held in shape by regular hydrogen bonds between the backbone carbonyl oxygen of one residue and the backbone amide hydrogen four residues ahead. This needs the backbone to sit in a fairly fixed, rigid geometry with regular phi and psi angles.

Step 2: Recall which amino acid resists this geometry.
Glycine has only a hydrogen atom as its side chain, the smallest possible side chain. This gives its backbone far more rotational freedom than any other amino acid, so it does not settle easily into the fixed phi and psi angles an alpha helix needs. Because of this, glycine is known as a helix breaker, alongside proline.

Step 3: Check why the other options do not break the helix.
Alanine has a small, simple methyl side chain and is actually one of the best helix formers, it fits the regular helical geometry easily.
Aspartic acid has a negatively charged side chain, it can sit inside a helix, though runs of like charges can sometimes cause local strain, it is not a classic helix breaker like glycine.
Tyrosine has a bulky aromatic side chain, this can cause some steric crowding but tyrosine is still commonly found within helices and is not considered a strong helix breaker.

Step 4: Final answer.
Glycine's extra backbone flexibility is what most disrupts the rigid, repeating geometry of an alpha helix, so introducing glycine into a helical region is most likely to break it.