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dc.contributor.authorCarrara, Guiaen
dc.contributor.authorSaraiva, Nunoen
dc.contributor.authorParsons, Maddyen
dc.contributor.authorByrne, Bernadetteen
dc.contributor.authorProle, Daviden
dc.contributor.authorTaylor, Colinen
dc.contributor.authorSmith, Geoffreyen
dc.date.accessioned2015-05-20T14:31:58Z
dc.date.available2015-05-20T14:31:58Z
dc.date.issued2015-05-01en
dc.identifier.citationThe Journal of Biological Chemistry, 290, 11785-11801. DOI: 10.1074/jbc.M115.637306en
dc.identifier.issn0021-9258
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/247867
dc.description.abstractGolgi anti-apoptotic proteins (GAAPs) are multitransmembrane proteins that are expressed in the Golgi apparatus and are able to homo-oligomerize. They are highly conserved throughout eukaryotes and are present in some prokaryotes and orthopoxviruses. Within eukaryotes, GAAPs regulate the Ca(2+) content of intracellular stores, inhibit apoptosis, and promote cell adhesion and migration. Data presented here demonstrate that purified viral GAAPs (vGAAPs) and human Bax inhibitor 1 form ion channels and that vGAAP from camelpox virus is selective for cations. Mutagenesis of vGAAP, including some residues conserved in the recently solved structure of a related bacterial protein, BsYetJ, altered the conductance (E207Q and D219N) and ion selectivity (E207Q) of the channel. Mutation of residue Glu-207 or -178 reduced the effects of GAAP on cell migration and adhesion without affecting protection from apoptosis. In contrast, mutation of Asp-219 abrogated the anti-apoptotic activity of GAAP but not its effects on cell migration and adhesion. These results demonstrate that GAAPs are ion channels and define residues that contribute to the ion-conducting pore and affect apoptosis, cell adhesion, and migration independently.
dc.description.sponsorshipThis work was supported by the United Kingdom Medical Research Council, the Biotechnology and Biological Sciences Research Council, and the Wellcome Trust
dc.languageengen
dc.language.isoenen
dc.publisherAmerican Society for Biochemistry and Molecular Biology Inc.
dc.rightsAttribution 2.0 UK: England & Wales*
dc.rights.urihttp://creativecommons.org/licenses/by/2.0/uk/*
dc.subjectElectrophysiologyen
dc.subjectIon Channelen
dc.subjectLipid Bilayeren
dc.subjectMembrane Proteinen
dc.subjectViral Proteinen
dc.subjectAmino Acid Sequenceen
dc.subjectAnimalsen
dc.subjectApoptosisen
dc.subjectCell Lineen
dc.subjectCell Movementen
dc.subjectConserved Sequenceen
dc.subjectHumansen
dc.subjectIon Channelsen
dc.subjectModels, Molecularen
dc.subjectMolecular Sequence Dataen
dc.subjectMutationen
dc.subjectPorosityen
dc.subjectProtein Conformationen
dc.titleGolgi anti-apoptotic proteins are highly conserved ion channels that affect apoptosis and cell migration.en
dc.typeArticle
prism.endingPage11801
prism.issueIdentifier18en
prism.publicationDate2015en
prism.publicationNameJournal of Biological Chemistryen
prism.startingPage11785
prism.volume290en
dc.rioxxterms.funderMRC
dc.rioxxterms.funderBBSRC
dc.rioxxterms.funderWellcome Trust
dcterms.dateAccepted2015-02-23en
rioxxterms.versionofrecord10.1074/jbc.M115.637306en
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by/4.0/en
rioxxterms.licenseref.startdate2015-05-01en
dc.contributor.orcidProle, David [0000-0003-2782-6665]
dc.contributor.orcidTaylor, Colin [0000-0001-7771-1044]
dc.contributor.orcidSmith, Geoffrey [0000-0002-3730-9955]
dc.identifier.eissn1083-351X
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idBBSRC (BB/L000075/1)
pubs.funder-project-idMRC (G0900224)
pubs.funder-project-idWellcome Trust (101844/Z/13/Z)
cam.issuedOnline2015-02-24en


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Attribution 2.0 UK: England & Wales
Except where otherwise noted, this item's licence is described as Attribution 2.0 UK: England & Wales