Entropic allostery dominates the phosphorylation-dependent regulation of Syk tyrosine kinase release from immunoreceptor tyrosine-based activation motifs.

ABSTRACT: Spleen tyrosine kinase (Syk) is an essential player in immune signaling through its ability to couple multiple classes of membrane immunoreceptors to intracellular signaling pathways. Ligand binding leads to the recruitment of Syk to a phosphorylated cytoplasmic region of the receptors called ITAM. Syk binds to ITAM with high-affinity (nanomolar K_d ) via its tandem pair of SH2 domains. The affinity between Syk and ITAM is allosterically regulated by phosphorylation at Y130 in a linker connecting the tandem SH2 domains; when Y130 is phosphorylated, the binding affinity decreases (micromolar K_d ). Previous equilibrium binding studies attribute the increase in the binding free energy to an intra-molecular binding (isomerization) step of the tandem SH2 and ITAM, but a phy

SUBMITTER: Feng C 

PROVIDER: S-EPMC6225982 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature