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Publication Abstract from PubMed

DNA-binding response regulators of the OmpR/PhoB subfamily alternate between inactive and active conformational states, with the latter having enhanced DNA-binding affinity. Phosphorylation of an aspartate residue in the receiver domain, usually via phosphotransfer from a cognate histidine kinase, stabilizes the active conformation. Many of the available structures of inactive OmpR/PhoB family proteins exhibit extensive interfaces between the N-terminal receiver and C-terminal DNA-binding domains. These interfaces invariably involve the alpha4-beta5-alpha5 face of the receiver domain, the locus of the largest differences between inactive and active conformations and the surface that mediates dimerization of receiver domains in the active state. Structures of receiver domain dimers of DrrB, DrrD and MtrA have been determined and phosphorylation kinetics analyzed. Analysis of phosphotransfer from small molecule phosphodonors has revealed large differences in autophosphorylation rates among OmpR/PhoB response regulators. Response regulators with substantial domain interfaces exhibit slow rates of phosphorylation. Rates are greatly increased in isolated receiver domain constructs. Such differences are not observed between autophosphorylation rates of full-length and isolated receiver domain of a response regulator that lacks interdomain interfaces nor are they observed in histidine kinase-mediated phosphotransfer. These findings suggest that domain interfaces restrict receiver domain conformational dynamics, stabilizing an inactive conformation that is catalytically incompetent for phosphotransfer from small molecule phosphodonors. Inhibition of phosphotransfer by domain interfaces provides an explanation for the observation that some response regulators cannot be phosphorylated by small molecule phosphodonors in vitro and provides a potential mechanism for insulating some response regulators from small molecule-mediated phosphorylation in vivo.

Regulation of response regulator autophosphorylation through interdomain contacts.,Barbieri CM, Mack TR, Robinson VL, Miller MT, Stock AM J Biol Chem. 2010 Aug 11. PMID:20702407^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.