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dc.contributor.authorCrawley-Snowdon, Harriet
dc.contributor.authorYang, Ji-Chun
dc.contributor.authorZaccai, Nathan R.
dc.contributor.authorDavis, Luther J.
dc.contributor.authorWartosch, Lena
dc.contributor.authorHerman, Emily K.
dc.contributor.authorBright, Nicholas A.
dc.contributor.authorSwarbrick, James S.
dc.contributor.authorCollins, Brett M.
dc.contributor.authorJackson, Lauren P.
dc.contributor.authorSeaman, Matthew N. J.
dc.contributor.authorLuzio, J. Paul
dc.contributor.authorDacks, Joel B.
dc.contributor.authorNeuhaus, David
dc.contributor.authorOwen, David J.
dc.date.accessioned2021-10-06T15:46:04Z
dc.date.available2021-10-06T15:46:04Z
dc.date.issued2020-10-06
dc.date.submitted2020-01-28
dc.identifier.others41467-020-18773-2
dc.identifier.other18773
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/329040
dc.descriptionFunder: Discovery Grants from the Natural Sciences and Engineering Research Council of Canada (RES0043758, RES0046091)
dc.description.abstractAbstract: VARP and TBC1D5 are accessory/regulatory proteins of retromer-mediated retrograde trafficking from endosomes. Using an NMR/X-ray approach, we determined the structure of the complex between retromer subunit VPS29 and a 12 residue, four-cysteine/Zn++ microdomain, which we term a Zn-fingernail, two of which are present in VARP. Mutations that abolish VPS29:VARP binding inhibit trafficking from endosomes to the cell surface. We show that VARP and TBC1D5 bind the same site on VPS29 and can compete for binding VPS29 in vivo. The relative disposition of VPS29s in hetero-hexameric, membrane-attached, retromer arches indicates that VARP will prefer binding to assembled retromer coats through simultaneous binding of two VPS29s. The TBC1D5:VPS29 interaction is over one billion years old but the Zn-fingernail appears only in VARP homologues in the lineage directly giving rise to animals at which point the retromer/VARP/TBC1D5 regulatory network became fully established.
dc.languageen
dc.publisherNature Publishing Group UK
dc.subjectArticle
dc.subject/631/45
dc.subject/631/80/313/1776
dc.subject/631/535/878/1263
dc.subject/101
dc.subject/9
dc.subject/82/103
dc.subjectarticle
dc.titleMechanism and evolution of the Zn-fingernail required for interaction of VARP with VPS29
dc.typeArticle
dc.date.updated2021-10-06T15:46:03Z
prism.issueIdentifier1
prism.publicationNameNature Communications
prism.volume11
dc.identifier.doi10.17863/CAM.76485
dcterms.dateAccepted2020-09-08
rioxxterms.versionofrecord10.1038/s41467-020-18773-2
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidYang, Ji-Chun [0000-0003-1933-5372]
dc.contributor.orcidHerman, Emily K. [0000-0002-5327-0755]
dc.contributor.orcidBright, Nicholas A. [0000-0002-2791-6727]
dc.contributor.orcidCollins, Brett M. [0000-0002-6070-3774]
dc.contributor.orcidJackson, Lauren P. [0000-0002-3705-6126]
dc.contributor.orcidSeaman, Matthew N. J. [0000-0001-9916-3245]
dc.contributor.orcidLuzio, J. Paul [0000-0003-3912-9760]
dc.contributor.orcidDacks, Joel B. [0000-0003-4520-5694]
dc.contributor.orcidNeuhaus, David [0000-0002-8561-7485]
dc.contributor.orcidOwen, David J. [0000-0002-8351-6322]
dc.identifier.eissn2041-1723
pubs.funder-project-idWellcome Trust (Wellcome) (090909/Z/09/Z)
pubs.funder-project-idRCUK | Medical Research Council (MRC) (MR/R009015/1)
pubs.funder-project-idRCUK | MRC | Medical Research Foundation (U105178934)
pubs.funder-project-idDepartment of Health | National Health and Medical Research Council (NHMRC) (APP1136021, APP1156493)
pubs.funder-project-idU.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) (R35GM119525)


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