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dc.contributor.authorAshenberg, Orr
dc.contributor.authorRozen-Gagnon, Kathryn
dc.contributor.authorKeating, Amy E.
dc.contributor.authorLaub, Michael T
dc.date.accessioned2015-10-02T17:24:18Z
dc.date.available2015-10-02T17:24:18Z
dc.date.issued2011-08
dc.date.submitted2011-08
dc.identifier.issn00222836
dc.identifier.issn1089-8638
dc.identifier.urihttp://hdl.handle.net/1721.1/99134
dc.description.abstractTwo-component signal transduction pathways consisting of a histidine kinase and a response regulator are used by prokaryotes to respond to diverse environmental and intracellular stimuli. Most species encode numerous paralogous histidine kinases that exhibit significant structural similarity. Yet in almost all known examples, histidine kinases are thought to function as homodimers. We investigated the molecular basis of dimerization specificity, focusing on the model histidine kinase EnvZ and RstB, its closest paralog in Escherichia coli. Direct binding studies showed that the cytoplasmic domains of these proteins each form specific homodimers in vitro. Using a series of chimeric proteins, we identified specificity determinants at the base of the four-helix bundle in the dimerization and histidine phosphotransfer domain. Guided by molecular coevolution predictions and EnvZ structural information, we identified sets of residues in this region that are sufficient to establish homospecificity. Mutating these residues in EnvZ to the corresponding residues in RstB produced a functional kinase that preferentially homodimerized over interacting with EnvZ. EnvZ and RstB likely diverged following gene duplication to yield two homodimers that cannot heterodimerize, and the mutants we identified represent possible evolutionary intermediates in this process.en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (Award GM067681)en_US
dc.description.sponsorshipNational Science Foundation (U.S.) (CAREER Grant)en_US
dc.description.sponsorshipNational Science Foundation (U.S.). Graduate Research Fellowshipen_US
dc.language.isoen_US
dc.publisherElsevieren_US
dc.relation.isversionofhttp://dx.doi.org/10.1016/j.jmb.2011.08.011en_US
dc.rightsCreative Commons Attribution-Noncommercial-NoDerivativesen_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/en_US
dc.sourcePMCen_US
dc.titleDeterminants of Homodimerization Specificity in Histidine Kinasesen_US
dc.typeArticleen_US
dc.identifier.citationAshenberg, Orr, Kathryn Rozen-Gagnon, Michael T. Laub, and Amy E. Keating. “Determinants of Homodimerization Specificity in Histidine Kinases.” Journal of Molecular Biology 413, no. 1 (October 2011): 222–235.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Computational and Systems Biology Programen_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biologyen_US
dc.contributor.mitauthorAshenberg, Orren_US
dc.contributor.mitauthorLaub, Michael T.en_US
dc.contributor.mitauthorKeating, Amy E.en_US
dc.relation.journalJournal of Molecular Biologyen_US
dc.eprint.versionAuthor's final manuscripten_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsAshenberg, Orr; Rozen-Gagnon, Kathryn; Laub, Michael T.; Keating, Amy E.en_US
dc.identifier.orcidhttps://orcid.org/0000-0002-8288-7607
dc.identifier.orcidhttps://orcid.org/0000-0003-4074-8980
mit.licensePUBLISHER_CCen_US
mit.metadata.statusComplete


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