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dc.contributor.authorLi, Jingen_US
dc.contributor.authorSu, Yangen_US
dc.contributor.authorXia, Weien_US
dc.contributor.authorQin, Yanen_US
dc.contributor.authorHumphries, Martin Jen_US
dc.contributor.authorVestweber, Dietmaren_US
dc.contributor.authorCabañas, Carlosen_US
dc.contributor.authorLu, Chafenen_US
dc.contributor.authorSpringer, Timothy Aen_US
dc.date.accessioned2017-04-06T03:19:24Z
dc.date.issued2017en_US
dc.identifier.citationLi, Jing, Yang Su, Wei Xia, Yan Qin, Martin J Humphries, Dietmar Vestweber, Carlos Cabañas, Chafen Lu, and Timothy A Springer. 2017. “Conformational equilibria and intrinsic affinities define integrin activation.” The EMBO Journal 36 (5): 629-645. doi:10.15252/embj.201695803. http://dx.doi.org/10.15252/embj.201695803.en
dc.identifier.issnen
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:32072077
dc.description.abstractAbstract We show that the three conformational states of integrin α5β1 have discrete free energies and define activation by measuring intrinsic affinities for ligand of each state and the equilibria linking them. The 5,000‐fold higher affinity of the extended‐open state than the bent‐closed and extended‐closed states demonstrates profound regulation of affinity. Free energy requirements for activation are defined with protein fragments and intact α5β1. On the surface of K562 cells, α5β1 is 99.8% bent‐closed. Stabilization of the bent conformation by integrin transmembrane and cytoplasmic domains must be overcome by cellular energy input to stabilize extension. Following extension, headpiece opening is energetically favored. N‐glycans and leg domains in each subunit that connect the ligand‐binding head to the membrane repel or crowd one another and regulate conformational equilibria in favor of headpiece opening. The results suggest new principles for regulating signaling in the large class of receptors built from extracellular domains in tandem with single‐span transmembrane domains.en
dc.language.isoen_USen
dc.publisherJohn Wiley and Sons Inc.en
dc.relation.isversionofdoi:10.15252/embj.201695803en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC5331762/pdf/en
dash.licenseLAAen_US
dc.subjectArticleen
dc.subjectaffinityen
dc.subjectconformationen
dc.subjectintegrinen
dc.subjectN‐glycanen
dc.subjectthermodynamicsen
dc.subjectCell Adhesion, Polarity & Cytoskeletonen
dc.subjectStructural Biologyen
dc.titleConformational equilibria and intrinsic affinities define integrin activationen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalThe EMBO Journalen
dash.depositing.authorLi, Jingen_US
dc.date.available2017-04-06T03:19:24Z
dc.identifier.doi10.15252/embj.201695803*
dash.contributor.affiliatedQin, Yan
dash.contributor.affiliatedSu, Yang
dash.contributor.affiliatedLu, Chafen
dash.contributor.affiliatedLi, Jing
dash.contributor.affiliatedSpringer, Timothy


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