Computational modeling of unphosphorylated CtrA:Cori binding in the Caulobacter cell cycle

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dc.contributor.authorWeston, Bronson R.en
dc.contributor.authorTyson, John J.en
dc.contributor.authorCao, Yangen
dc.date.accessioned2022-09-02T19:36:39Zen
dc.date.available2022-09-02T19:36:39Zen
dc.date.issued2021-12-17en
dc.description.abstractIn the alphaproteobacterium, Caulobacter crescentus, phosphorylated CtrA (CtrA similar to P), a master regulatory protein, binds directly to the chromosome origin (Cori) to inhibit DNA replication. Using a mathematical model of CtrA binding at Cori site [d], we provide computational evidence that CtrA(U) can disc ace CtrA similar to P from Cori at the G1-S transition. Investigation of this interaction within a detailed model of the C. crescentus cell cycle suggests that CckA phosphatase may clear Cori of CtrA similar to P by altering the [CtrA(U)]/[CtrA similar to P] ratio rather than by completely depleting CtrA similar to P. Model analysis reveals that the mechanism allows for a speedier transition into S phase, stabilizes the timing of chromosome replication under fluctuating rates of CtrA proteolysis, and may contribute to the viability of numerous mutant strains. Overall, these results suggest that CtrA(U) enhances the robustness of chromosome replication. More generally, our proposed regulation of CtrA:Cori dynamics may represent a novel motif for molecular signaling in cell physiology.en
dc.description.notesThis work was partially supported by the National Science Foundation (NSF) under awards CCF-1526666, MCB-1613741, and CCF-1909122. The funding sources played no role in the design of the study, in the collection, analysis, and interpretation of data, and in writing the manuscript.en
dc.description.sponsorshipNational Science Foundation (NSF) [CCF-1526666, MCB-1613741, CCF-1909122]en
dc.description.versionPublished versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1016/j.isci.2021.103413en
dc.identifier.eissn2589-0042en
dc.identifier.issue12en
dc.identifier.other103413en
dc.identifier.pmid34901785en
dc.identifier.urihttp://hdl.handle.net/10919/111698en
dc.identifier.volume24en
dc.language.isoenen
dc.publisherCell Pressen
dc.rightsCreative Commons Attribution-NonCommercial-NoDerivatives 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/en
dc.subjectchromosome-replication originen
dc.subjectresponse regulator ctraen
dc.subjectdna-replicationen
dc.subjecthistidine kinaseen
dc.subjectpolar localizationen
dc.subjectallosteric controlen
dc.subjectprotease complexen
dc.subjecttemporal controlen
dc.subjectfeedback-controlen
dc.subjectsystems biologyen
dc.titleComputational modeling of unphosphorylated CtrA:Cori binding in the Caulobacter cell cycleen
dc.title.serialiScienceen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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