Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/146721
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dc.contributor.authorBu, Wentingen_US
dc.contributor.authorLevitskaya, Zarinaen_US
dc.contributor.authorLoh, Zhi Yangen_US
dc.contributor.authorJin, Shengyangen_US
dc.contributor.authorBasu, Shibomen_US
dc.contributor.authorEro, Ryaen_US
dc.contributor.authorYan, Xinfuen_US
dc.contributor.authorWang, Meitianen_US
dc.contributor.authorNgan, So Fong Camen_US
dc.contributor.authorSze, Siu Kwanen_US
dc.contributor.authorTan, Suet-Mienen_US
dc.contributor.authorGao, Yong-Guien_US
dc.date.accessioned2021-03-08T08:29:11Z-
dc.date.available2021-03-08T08:29:11Z-
dc.date.issued2020-
dc.identifier.citationBu, W., Levitskaya, Z., Loh, Z. Y., Jin, S., Basu, S., Ero, R., ... Gao, Y.-G. (2020). Structural basis of human full-length kindlin-3 homotrimer in an auto-inhibited state. PLOS Biology, 18(7): e3000755-. doi:10.1371/journal.pbio.3000755en_US
dc.identifier.issn1545-7885en_US
dc.identifier.urihttps://hdl.handle.net/10356/146721-
dc.description.abstractKindlin-1, -2, and -3, directly bind integrin β cytoplasmic tails to regulate integrin activation and signaling. Despite their functional significance and link to several diseases, structural information on full-length kindlin proteins remains unknown. Here, we report the crystal structure of human full-length kindlin-3, which reveals a novel homotrimer state. Unlike kindlin-3 monomer, which is the major population in insect and mammalian cell expression systems, kindlin-3 trimer does not bind integrin β cytoplasmic tail as the integrin-binding pocket in the F3 sub-domain of one protomer is occluded by the PH domain of another protomer, suggesting that kindlin-3 is auto-inhibited upon trimer formation. This is also supported by functional assays in which kindlin-3 knockout K562 erythroleukemia cells re-constituted with the mutant kindlin-3 containing trimer-disrupting mutations exhibited an increase in integrin-mediated adhesion and spreading on fibronectin compared to those re-constituted with wild type kindlin-3. Taken together, our findings reveal a novel mechanism of kindlin auto-inhibition that involves its homotrimer formation.en_US
dc.language.isoenen_US
dc.relation.ispartofPLOS Biologyen_US
dc.rights© 2020 Bu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_US
dc.subjectScience::Biological sciencesen_US
dc.titleStructural basis of human full-length kindlin-3 homotrimer in an auto-inhibited stateen_US
dc.typeJournal Articleen
dc.contributor.schoolSchool of Biological Sciencesen_US
dc.contributor.researchNTU Institute of Structural Biologyen_US
dc.identifier.doi10.1371/journal.pbio.3000755-
dc.description.versionPublished versionen_US
dc.identifier.issue7en_US
dc.identifier.volume18en_US
dc.identifier.spagee3000755en_US
dc.subject.keywordsKindlinen_US
dc.subject.keywordsFERMen_US
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