The Goldbeter-Koshland Switch in the First-Order Region and Its Response to Dynamic Disorder

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dc.contributor.authorXing, Jianhuaen
dc.contributor.authorChen, Jingen
dc.contributor.departmentBiological Sciencesen
dc.date.accessioned2018-11-15T14:43:30Zen
dc.date.available2018-11-15T14:43:30Zen
dc.date.issued2008-05-14en
dc.description.abstractIn their classical work (Proc. Natl. Acad. Sci. USA, 1981, 78:6840–6844), Goldbeter and Koshland mathematically analyzed a reversible covalent modification system which is highly sensitive to the concentration of effectors. Its signal-response curve appears sigmoidal, constituting a biochemical switch. However, the switch behavior only emerges in the ‘zero-order region’, i.e. when the signal molecule concentration is much lower than that of the substrate it modifies. In this work we showed that the switching behavior can also occur under comparable concentrations of signals and substrates, provided that the signal molecules catalyze the modification reaction in cooperation. We also studied the effect of dynamic disorders on the proposed biochemical switch, in which the enzymatic reaction rates, instead of constant, appear as stochastic functions of time. We showed that the system is robust to dynamic disorder at bulk concentration. But if the dynamic disorder is quasi-static, large fluctuations of the switch response behavior may be observed at low concentrations. Such fluctuation is relevant to many biological functions. It can be reduced by either increasing the conformation interconversion rate of the protein, or correlating the enzymatic reaction rates in the network.en
dc.description.versionPublished versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1371/journal.pone.0002140en
dc.identifier.eissn1932-6203en
dc.identifier.issue5en
dc.identifier.othere2140en
dc.identifier.pmid18478088en
dc.identifier.urihttp://hdl.handle.net/10919/85854en
dc.identifier.volume3en
dc.language.isoenen
dc.publisherPLOSen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.titleThe Goldbeter-Koshland Switch in the First-Order Region and Its Response to Dynamic Disorderen
dc.title.serialPLOS ONEen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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