Show simple item record

dc.contributor.authorAmin, Muniaen
dc.contributor.authorKothamachu, Varun B.en
dc.contributor.authorFeliu, Elisendaen
dc.contributor.authorScharf, Birgit E.en
dc.contributor.authorPorter, Steven L.en
dc.contributor.authorSoyer, Orkun S.en
dc.date.accessioned2017-12-18T18:37:14Zen
dc.date.available2017-12-18T18:37:14Zen
dc.date.issued2014-10-01en
dc.identifier.issn1553-734Xen
dc.identifier.urihttp://hdl.handle.net/10919/81266en
dc.description.abstractSynthetic biology aims to design de novo biological systems and reengineer existing ones. These efforts have mostly focused on transcriptional circuits, with reengineering of signaling circuits hampered by limited understanding of their systems dynamics and experimental challenges. Bacterial two-component signaling systems offer a rich diversity of sensory systems that are built around a core phosphotransfer reaction between histidine kinases and their output response regulator proteins, and thus are a good target for reengineering through synthetic biology. Here, we explore the signalresponse relationship arising from a specific motif found in two-component signaling. In this motif, a single histidine kinase (HK) phosphotransfers reversibly to two separate output response regulator (RR) proteins. We show that, under the experimentally observed parameters from bacteria and yeast, this motif not only allows rapid signal termination, whereby one of the RRs acts as a phosphate sink towards the other RR (i.e. the output RR), but also implements a sigmoidal signalresponse relationship. We identify two mathematical conditions on system parameters that are necessary for sigmoidal signal-response relationships and define key parameters that control threshold levels and sensitivity of the signal-response curve. We confirm these findings experimentally, by in vitro reconstitution of the one HK-two RR motif found in the Sinorhizobium meliloti chemotaxis pathway and measuring the resulting signal-response curve. We find that the level of sigmoidality in this system can be experimentally controlled by the presence of the sink RR, and also through an auxiliary protein that is shown to bind to the HK (yielding Hill coefficients of above 7). These findings show that the one HK-two RR motif allows bacteria and yeast to implement tunable switch-like signal processing and provides an ideal basis for developing threshold devices for synthetic biology applications.en
dc.format.extent? - ? (11) page(s)en
dc.languageEnglishen
dc.publisherPLOSen
dc.relation.urihttp://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000344547900039&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=930d57c9ac61a043676db62af60056c1en
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectBiochemical Research Methodsen
dc.subjectMathematical & Computational Biologyen
dc.subjectBiochemistry & Molecular Biologyen
dc.subjectRHODOBACTER-SPHAEROIDES CHEMOTAXISen
dc.subjectKINASE KINASE KINASEen
dc.subjectESCHERICHIA-COLIen
dc.subjectRESPONSE REGULATORen
dc.subjectSYNTHETIC BIOLOGYen
dc.subjectHISTIDINE KINASESen
dc.subjectTRANSDUCTIONen
dc.subjectCELLen
dc.subjectPHOSPHOTRANSFERen
dc.subjectSPECIFICITYen
dc.titlePhosphate Sink Containing Two-Component Signaling Systems as Tunable Threshold Devicesen
dc.typeArticle - Refereeden
dc.description.versionPublished (Publication status)en
dc.contributor.departmentBiological Sciencesen
dc.title.serialPLOS COMPUTATIONAL BIOLOGYen
dc.identifier.doihttps://doi.org/10.1371/journal.pcbi.1003890en
dc.identifier.volume10en
dc.identifier.issue10en
dc.identifier.orcidScharf, BE [0000-0001-6271-8972]en
dc.identifier.eissn1553-7358en
pubs.organisational-group/Virginia Techen
pubs.organisational-group/Virginia Tech/All T&R Facultyen
pubs.organisational-group/Virginia Tech/Faculty of Health Sciencesen
pubs.organisational-group/Virginia Tech/Scienceen
pubs.organisational-group/Virginia Tech/Science/Biological Sciencesen
pubs.organisational-group/Virginia Tech/Science/COS T&R Facultyen
pubs.organisational-group/Virginia Tech/University Research Institutesen
pubs.organisational-group/Virginia Tech/University Research Institutes/Fralin Life Sciencesen
pubs.organisational-group/Virginia Tech/University Research Institutes/Fralin Life Sciences/Fralin Affiliated Facultyen


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record

Creative Commons Attribution 4.0 International
License: Creative Commons Attribution 4.0 International