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Article: Ras activation by SOS: Allosteric regulation by altered fluctuation dynamics

TitleRas activation by SOS: Allosteric regulation by altered fluctuation dynamics
Authors
Issue Date2014
Citation
Science, 2014, v. 345, n. 6192, p. 50-54 How to Cite?
AbstractActivation of the small guanosine triphosphatase H-Ras by the exchange factor Son of Sevenless (SOS) is an important hub for signal transduction. Multiple layers of regulation, through protein and membrane interactions, govern activity of SOS. We characterized the specific activity of individual SOS molecules catalyzing nucleotide exchange in H-Ras. Single-molecule kinetic traces revealed that SOS samples a broad distribution of turnover rates through stochastic fluctuations between distinct, long-lived (more than 100 seconds), functional states. The expected allosteric activation of SOS by Ras-guanosine triphosphate (GTP) was conspicuously absent in the mean rate. However, fluctuations into highly active states were modulated by Ras-GTP. This reveals a mechanism in which functional output may be determined by the dynamical spectrum of rates sampled by a small number of enzymes, rather than the ensemble average.
Persistent Identifierhttp://hdl.handle.net/10722/202223
ISSN
2015 Impact Factor: 34.661
2015 SCImago Journal Rankings: 13.217
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorIversen, Lars Fogh-
dc.contributor.authorTu, Hsiunglin-
dc.contributor.authorLin, Wanchen-
dc.contributor.authorChristensen, Sune M.-
dc.contributor.authorAbel, Steven M.-
dc.contributor.authorIwig, Jeffrey S.-
dc.contributor.authorWu, Hungjen-
dc.contributor.authorGureasko, Jodi M.-
dc.contributor.authorRhodes, Christopher P.-
dc.contributor.authorPetit, Rebecca S.-
dc.contributor.authorHansen, Scott D.-
dc.contributor.authorThill, Peter D.-
dc.contributor.authorYu, Chenghan-
dc.contributor.authorStamou, Dimitrios G.-
dc.contributor.authorChakraborty, Arup K.-
dc.contributor.authorKuriyan, John-
dc.contributor.authorGroves, Jay T.-
dc.date.accessioned2014-08-22T02:57:49Z-
dc.date.available2014-08-22T02:57:49Z-
dc.date.issued2014-
dc.identifier.citationScience, 2014, v. 345, n. 6192, p. 50-54-
dc.identifier.issn0036-8075-
dc.identifier.urihttp://hdl.handle.net/10722/202223-
dc.description.abstractActivation of the small guanosine triphosphatase H-Ras by the exchange factor Son of Sevenless (SOS) is an important hub for signal transduction. Multiple layers of regulation, through protein and membrane interactions, govern activity of SOS. We characterized the specific activity of individual SOS molecules catalyzing nucleotide exchange in H-Ras. Single-molecule kinetic traces revealed that SOS samples a broad distribution of turnover rates through stochastic fluctuations between distinct, long-lived (more than 100 seconds), functional states. The expected allosteric activation of SOS by Ras-guanosine triphosphate (GTP) was conspicuously absent in the mean rate. However, fluctuations into highly active states were modulated by Ras-GTP. This reveals a mechanism in which functional output may be determined by the dynamical spectrum of rates sampled by a small number of enzymes, rather than the ensemble average.-
dc.languageeng-
dc.relation.ispartofScience-
dc.titleRas activation by SOS: Allosteric regulation by altered fluctuation dynamics-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1126/science.1250373-
dc.identifier.pmid24994643-
dc.identifier.pmcidPMC4255705-
dc.identifier.scopuseid_2-s2.0-84903699445-
dc.identifier.hkuros242891-
dc.identifier.volume345-
dc.identifier.issue6192-
dc.identifier.spage50-
dc.identifier.epage54-
dc.identifier.eissn1095-9203-
dc.identifier.isiWOS:000338284400045-
dc.identifier.f1000718478044-

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