Spleen tyrosine kinase (Syk), an essential protein in immune signaling, binds activated membrane immune receptors with high affinity (nanomolar <i>K<sub>D</sub></i>). Once phosphorylated on a linker tyrosine residue, Syk affinity for receptors is decreased 100- to 1000-fold, which promotes termination of membrane signaling and/or the availability of Syk to function in cytoplasmic processes. The talk will focus on the physical mechanism for decreased affinity upon phosphorylation. Results from molecular dynamics simulations, solution-state NMR and calorimetry experiments support a mechanism driven primarily by entropy that derives from modifications in electrostatic interactions of solvent-exposed Syk residues. That the regulation of binding by protein phosphorylation lacks a significant enthalpic component is unique to Syk, to our knowledge.

Regulating protein-protein interactions by phosphorylation: New mechanism involving solvated electrostatic interactions

2019 Fall National Meeting

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