title: Cell fate regulation governed by a repurposed bacterial histidine kinase.
abstract: One of the simplest organisms to divide asymmetrically is the bacterium Caulobacter crescentus. The DivL pseudo-histidine kinase, positioned at one cell pole, regulates cell-fate by controlling the activation of the global transcription factor CtrA via an interaction with the response regulator (RR) DivK. DivL uniquely contains a tyrosine at the histidine phosphorylation site, and can achieve these regulatory functions in vivo without kinase activity. Determination of the DivL crystal structure and biochemical analysis of wild-type and site-specific DivL mutants revealed that the DivL PAS domains regulate binding specificity for DivK∼P over DivK, which is modulated by an allosteric intramolecular interaction between adjacent domains. We discovered that DivL's catalytic domains have been repurposed as a phosphospecific RR input sensor, thereby reversing the flow of information observed in conventional histidine kinase (HK)-RR systems and coupling a complex network of signaling proteins for cell-fate regulation.
authors.affiliation: Department of Developmental Biology, Stanford University School of Medicine, Stanford, California, United States of America.
authors.forename: W Seth
authors.initials: WS
authors.lastname: Childers
authors.affiliation: Stanford Synchrotron Radiation Lightsource, SLAC National Accelerator Laboratory, Menlo Park, California, United States of America; Joint Center for Structural Genomics, United States of America.
authors.forename: Qingping
authors.initials: Q
authors.lastname: Xu
authors.affiliation: Department of Developmental Biology, Stanford University School of Medicine, Stanford, California, United States of America.
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Mann
authors.affiliation: Stanford Synchrotron Radiation Lightsource, SLAC National Accelerator Laboratory, Menlo Park, California, United States of America.
authors.forename: Irimpan I
authors.initials: II
authors.lastname: Mathews
authors.affiliation: Department of Developmental Biology, Stanford University School of Medicine, Stanford, California, United States of America.
authors.forename: Jimmy A
authors.initials: JA
authors.lastname: Blair
authors.affiliation: Stanford Synchrotron Radiation Lightsource, SLAC National Accelerator Laboratory, Menlo Park, California, United States of America; Joint Center for Structural Genomics, United States of America.
authors.forename: Ashley M
authors.initials: AM
authors.lastname: Deacon
authors.affiliation: Department of Developmental Biology, Stanford University School of Medicine, Stanford, California, United States of America.
authors.forename: Lucy
authors.initials: L
authors.lastname: Shapiro
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism*; D016935:Caulobacter crescentus / Q000378:metabolism*; D002453:Cell Cycle; D019281:Dimerization; D000071677:Histidine Kinase; D011485:Protein Binding; D011494:Protein Kinases / Q000378:metabolism*; D017434:Protein Structure, Tertiary
chemical_list: D001426:Bacterial Proteins; C095478:DivK protein, Caulobacter crescentus; D011494:Protein Kinases; D000071677:Histidine Kinase