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dc.contributor.authorBurgess, Selena G
dc.contributor.authorMukherjee, Manjeet
dc.contributor.authorSabir, Sarah
dc.contributor.authorJoseph, Nimesh
dc.contributor.authorGutiérrez-Caballero, Cristina
dc.contributor.authorRichards, Mark W
dc.contributor.authorHuguenin-Dezot, Nicolas
dc.contributor.authorChin, Jason
dc.contributor.authorKennedy, Eileen J
dc.contributor.authorPfuhl, Mark
dc.contributor.authorRoyle, Stephen J
dc.contributor.authorGergely, Fanni
dc.contributor.authorBayliss, Richard
dc.date.accessioned2018-07-05T13:26:32Z
dc.date.available2018-07-05T13:26:32Z
dc.date.issued2018-04-13
dc.identifier.issn0261-4189
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/277840
dc.description.abstractAurora-A regulates the recruitment of TACC3 to the mitotic spindle through a phospho-dependent interaction with clathrin heavy chain (CHC). Here, we describe the structural basis of these interactions, mediated by three motifs in a disordered region of TACC3. A hydrophobic docking motif binds to a previously uncharacterized pocket on Aurora-A that is blocked in most kinases. Abrogation of the docking motif causes a delay in late mitosis, consistent with the cellular distribution of Aurora-A complexes. Phosphorylation of Ser558 engages a conformational switch in a second motif from a disordered state, needed to bind the kinase active site, into a helical conformation. The helix extends into a third, adjacent motif that is recognized by a helical-repeat region of CHC, not a recognized phospho-reader domain. This potentially widespread mechanism of phospho-recognition provides greater flexibility to tune the molecular details of the interaction than canonical recognition motifs that are dominated by phosphate binding.
dc.format.mediumPrint-Electronic
dc.languageeng
dc.language.isoen
dc.publisherEMBO
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectCell Line
dc.subjectHumans
dc.subjectMicrotubule-Associated Proteins
dc.subjectSpindle Apparatus
dc.subjectAurora Kinase A
dc.subjectProtein Conformation, alpha-Helical
dc.titleMitotic spindle association of TACC3 requires Aurora-A-dependent stabilization of a cryptic α-helix.
dc.typeArticle
prism.issueIdentifier8
prism.publicationDate2018
prism.publicationNameEMBO J
prism.volume37
dc.identifier.doi10.17863/CAM.25176
dcterms.dateAccepted2018-02-02
rioxxterms.versionofrecord10.15252/embj.201797902
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2018-04
dc.contributor.orcidChin, Jason [0000-0003-1219-4757]
dc.contributor.orcidPfuhl, Mark [0000-0001-9592-6639]
dc.contributor.orcidRoyle, Stephen J [0000-0001-8927-6967]
dc.contributor.orcidGergely, Fanni [0000-0002-2441-8095]
dc.contributor.orcidBayliss, Richard [0000-0003-0604-2773]
dc.identifier.eissn1460-2075
rioxxterms.typeJournal Article/Review
pubs.funder-project-idCancer Research UK (CB4180)
pubs.funder-project-idCancer Research UK (C14303/A17197)
cam.issuedOnline2018-03-06


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International