Question

ONLY ANSWER IF YOU KNOW!

The reorganization of protein domains often elicits the architectural impetus for signal initiation in biological systems. For instance, the MAP kinase, Cdk2, has three Arg residues at positions 50, 126, and 150, and a Thr residue at position 160. If no post- translational modifications occur on any of the four amino acid residues, no interaction occurs. However, if the Thr residue is phosphorylated, structural rearrangement occurs to obtain the conformation shown below. Why does this rearrangement occur? Assume biological pH, 7.4. If the Thr residue is mutated to an alanine, what conformation do you think the protein would assume (meaning, one that looks like Thr, or one that looks like phosphor-Thr)?

Answer 1

The side-chain of arginine terminates in a guanidinium group, which has very high pK_a (~12.10). As a result, the side-chain of arginine is very basic in nature. Threonine is uncharged at physiological pH. Hence, arginine does not interact as readily with threonine as it does with phosphothreonine, where the phosphate group on phosphothreonine imparts it a very strong acidic character.

Alanine's side-chain cannot be phosphorylated (how disappointing!). Thus, if the threonine is mutated to alanine, the protein will behave like the one with threonine rather than the one with phosphothreonine (because arginine will not interact with uncharged alanine).