Question

Autophosphorylation is done on

• A. His residues
• B. Ser/Thr residues
• C. Cys residues
• D. Lys residues

Hint:

Histidine kinase autophosphorylation is crucial in bacterial signaling and differs from the typical phosphorylation of Ser/Thr in eukaryotic kinases.

Answer 1

The Correct Option is A

Autophosphorylation here refers to the self-phosphorylation step seen in histidine kinase systems, where the kinase transfers a phosphate onto its own histidine residue before relaying it onward to a response regulator.

Cys and Lys side chains are used for other modifications (disulfide bonds, ubiquitination) rather than phosphate acceptance, and Ser/Thr phosphorylation describes substrate phosphorylation by a kinase acting on a different protein, not the kinase acting on itself in this system.

So autophosphorylation in this context occurs on His residues.

Answer 2

Comparing the chemical stability and type of phosphoamino acid bond each residue would form clarifies the answer.

1. His residues: Phosphorylation on histidine forms a phosphoramidate bond, which is high-energy and labile -- exactly the kind of reversible, easily transferred phosphate linkage needed for a signalling kinase to autophosphorylate and then hand that phosphate off to another protein.
2. Ser/Thr residues: Phosphorylation here forms a stable phosphoester bond, well suited to marking a substrate protein for a lasting regulatory change, but a different type of chemistry from the transient phospho-relay autophosphorylation being described.
3. Cys residues: The thiol group of cysteine does not typically form a phosphoamino acid at all in standard kinase signalling.
4. Lys residues: The amine side chain of lysine is not the residue used for phosphate transfer in kinase autophosphorylation chemistry.

The high-energy, transferable phosphoramidate bond formed on histidine matches the relay-type autophosphorylation being asked about.

So, the correct answer is His residues.