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dc.contributor.authorBush, Martin
dc.contributor.authorAlhanshali, Bashir M
dc.contributor.authorQian, Shuo
dc.contributor.authorStanley, Christopher B
dc.contributor.authorHeller, William T
dc.contributor.authorMatsui, Tsutomu
dc.contributor.authorWeiss, Thomas M
dc.contributor.authorNicholl, Iain D
dc.contributor.authorWalz, Thomas
dc.contributor.authorCallaway, David JE
dc.contributor.authorBu, Zimei
dc.date.accessioned2019-11-06T11:50:02Z
dc.date.available2019-11-06T11:50:02Z
dc.date.issued2019-10-07
dc.identifier.citationBush, M., Alhanshali, B. M., Qian, S., Stanley, C. B., Heller, W. T., Matsui, T., Weiss, T. M., Nicholl, I. D., Walz, T., Callaway, D. J. E.and Bu, Z. (2019) An ensemble of flexible conformations underlies mechanotransduction by the cadherin-catenin adhesion complex, Proceedings of the National Academy of Sciences, 116(43), pp. 21545-21555.en
dc.identifier.issn0027-8424en
dc.identifier.doi10.1073/pnas.1911489116en
dc.identifier.urihttp://hdl.handle.net/2436/622912
dc.description© 2019 The Authors. Published by National Academy of Sciences. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1073/pnas.1911489116
dc.description.abstractThe cadherin–catenin adhesion complex is the central component of the cell–cell adhesion adherens junctions that transmit mechanical stress from cell to cell. We have determined the nanoscale structure of the adherens junction complex formed by the α-catenin•β-catenin•epithelial cadherin cytoplasmic domain (ABE) using negative stain electron microscopy, small-angle X-ray scattering, and selective deuteration/small-angle neutron scattering. The ABE complex is highly pliable and displays a wide spectrum of flexible structures that are facilitated by protein-domain motions in α- and β-catenin. Moreover, the 107-residue intrinsically disordered N-terminal segment of β-catenin forms a flexible “tongue” that is inserted into α-catenin and participates in the assembly of the ABE complex. The unanticipated ensemble of flexible conformations of the ABE complex suggests a dynamic mechanism for sensitivity and reversibility when transducing mechanical signals, in addition to the catch/slip bond behavior displayed by the ABE complex under mechanical tension. Our results provide mechanistic insight into the structural dynamics for the cadherin–catenin adhesion complex in mechanotransduction.en
dc.description.sponsorshipThis research was funded by NSF Grant MCB-1817684 (to Z.B.) and National Center for Research Resources Grant 2G12 RR003060 (to City College of New York). A portion of the research conducted at Oak Ridge National Laboratory’s Spallation Neutron Source and High Flux Isotope Reactor was sponsored by the Scientific User Facilities Division, Office of Basic Energy Sciences, US Department of Energy (DOE). The Bio-SANS of the Center for Structural Molecular Biology at the High Flux Isotope Reactor is supported by the Office of Biological and Environmental Research of the DOE. Use of the SSRL, Stanford Linear Accelerator Center’s is supported by DOE, Office of Science, Office of Basic Energy Sciences Contract DE-AC02-76SF00515. The SSRL Structural Molecular Biology Program is supported by the DOE Office of Biological and Environmental Research and NIH, National Institute of General Medical Sciences (NIGMS) Grant P41 GM103393.en
dc.formatapplication/pdfen
dc.languageen
dc.language.isoenen
dc.publisherProceedings of the National Academy of Sciencesen
dc.relation.urlhttps://www.pnas.org/content/116/43/21545en
dc.subjectadherens junctionen
dc.subjectmechanotransductionen
dc.subjectnegative stain electron microscopyen
dc.subjectsmall-angle X-ray scatteringen
dc.subjectsmall-angle neutron scatteringen
dc.titleAn ensemble of flexible conformations underlies mechanotransduction by the cadherin-catenin adhesion complexen
dc.typeJournal articleen
dc.identifier.eissn1091-6490
dc.identifier.journalProceedings of the National Academy of Sciencesen
dc.date.updated2019-10-31T12:23:30Z
dc.date.accepted2019-09-12
rioxxterms.funderJiscen
rioxxterms.identifier.projectMCB-1817684en
rioxxterms.identifier.project2G12 RR003060en
rioxxterms.identifier.projectDE-AC02-76SF00515en
rioxxterms.identifier.projectP41 GM103393en
rioxxterms.versionVoRen
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/en
rioxxterms.licenseref.startdate2019-11-06en
dc.source.volume116
dc.source.issue43
dc.source.beginpage21545
dc.source.endpage21555
dc.description.versionPublished version
refterms.dateFCD2019-11-06T11:48:15Z
refterms.versionFCDVoR
refterms.dateFOA2019-11-06T11:50:03Z


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