Question

One common motif for DNA binding proteins is the Helix-Turn-Helix motif, where the first helix fits in the major groove and the second helix makes contacts along the phosphate backbone to stabilize the helix in the major groove. If a mutation changes one of the recognition amino acids in the binding helix from a glutamic acid residue to a proline residue, what effect on binding would you predict? (you should imagine the amino acids in a peptide at physiological pH)

Answer 1

The question is incomplete as it does not have the options which are

A. no change since both amino acids are negatively charged

B. modest change because both amino acids carry a charge

C. modest change because both are about the same size

D. severe change because the amino acids are oppositely charged, one negative one positive

E. severe change because replacing the aspartic acid would severely alter the confirmation of the protein  and the protein would probably be degraded

Answer:

Option-E

Explanation:

The helix-turn-helix is the DNA binding motif which binds with the DNA binding domain and controls the gene expression. The helix-turn-helix binds the DNA as a dimer.

If a mutation in the gene which codes for the motif changes one amino acid that is glutamic acid to the proline it will alter the conformation of the protein.

The reason for this is that proline, when is present in the peptide, does not have the hydrogen ions to donate as a result of which it does not form the helix structure and thus helix structure will not be stabilized with this and the protein will be degraded.

Thus, Option-E is correct.