Cyclic di-GMP mediates a histidine kinase/phosphatase switch by noncovalent domain cross-linking.

ABSTRACT: Histidine kinases are key components of regulatory networks in bacteria. Although many of these enzymes are bifunctional, mediating both phosphorylation and dephosphorylation of downstream targets, the molecular details of this central regulatory switch are unclear. We showed recently that the universal second messenger cyclic di-guanosine monophosphate (c-di-GMP) drives Caulobacter crescentus cell cycle progression by forcing the cell cycle kinase CckA from its default kinase into phosphatase mode. We use a combination of structure determination, modeling, and functional analysis to demonstrate that c-di-GMP reciprocally regulates the two antagonistic CckA activities through noncovalent cross-linking of the catalytic domain with the dimerization histidine phosphotransfer (DHp) domain. We

SUBMITTER: Dubey BN 

PROVIDER: S-EPMC5026420 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature