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Speaker: Ranajeet Ghose
Topic: Functional Regulation of a Unique Family of Tyrosine Kinases
Abstract: BY-kinases represent a family of tyrosine kinases that are universally conserved in the bacterial kingdom but have no known eukaryotic or archaeal counterparts. BY-kinases deploy distinctive catalytic domains reminiscent of P-loop nucleoside triphosphatases in lieu of the classic dual-lobed fold characteristic of eukaryotic protein kinases. BY-kinase
genes most commonly occur in clusters that encode essential components of the synthesis, assembly, and export machinery of complex polysaccharides involved in biofilm or capsule formation. BY-kinases have been suggested to function through a cyclic process involving the assembly and disassembly of oligomeric species correlated with the overall phosphorylation level of a C-terminal cluster of tyrosine residues. However, the mechanisms that couple this process to functional states of the enzyme and integrate it into the complex machinery utilized to generate the polysaccharide product remain
unclear. Using data derived from a variety of computational and experimental
approaches, we postulate a mechanism that involves temporal coordination of the assembly/disassembly process with auto-kinase function of the enzyme and its ability to be dephosphorylated by its counteracting phosphatase. We speculate that this temporal control enables BY-kinases to act as molecular timers coordinating the diverse processes involved in the synthesis, polymerization, and export of complex sugar derivatives. We suggest that BY-kinases have adapted the ancient P-loop fold in unique fashion to phosphorylate on tyrosine and drive key physiological processes through exquisite spatiotemporal control over protein-protein interactions and conformational changes.