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dc.contributor.authorBao, Huanen
dc.contributor.authorGoldschen-Ohm, Marcelen
dc.contributor.authorJeggle, Piaen
dc.contributor.authorChanda, Baronen
dc.contributor.authorEdwardson, Michaelen
dc.contributor.authorChapman, Edwin Ren
dc.date.accessioned2015-12-08T17:50:08Z
dc.date.available2015-12-08T17:50:08Z
dc.date.issued2015-12-14en
dc.identifier.citationNature Structural and Molecular Biology 2015, 23: 67–73. doi:10.1038/nsmb.3141en
dc.identifier.issn1545-9993
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/252910
dc.description.abstractDuring exocytosis, fusion pores form the first aqueous connection that allows escape of neurotransmitters and hormones from secretory vesicles. Although it is well established that SNARE proteins catalyze fusion, the structure and composition of fusion pores remain unknown. Here, we exploited the rigid framework and defined size of nanodiscs to interrogate the properties of reconstituted fusion pores, using the neurotransmitter glutamate as a content-mixing marker. Efficient Ca²⁺-stimulated bilayer fusion, and glutamate release, occurred with approximately two molecules of mouse synaptobrevin 2 reconstituted into ~6-nm nanodiscs. The transmembrane domains of SNARE proteins assumed distinct roles in lipid mixing versus content release and were exposed to polar solvent during fusion. Additionally, tryptophan substitutions at specific positions in these transmembrane domains decreased glutamate flux. Together, these findings indicate that the fusion pore is a hybrid structure composed of both lipids and proteins.
dc.description.sponsorshipWe thank Gerhard Wagner for providing the MSP∆1D1H4-H6 plasmid. This study was supported by a grant from the US National Institutes of Health (MH061876). H.B. is supported by a postdoctoral fellowship from Human Frontier Science Program. B.C. and M.P.G are supported by funding from the US National Institutes of Health (R01 GM084140). P.J. is supported by Kidney Research UK. J.M.E. is supported by the Biotechnology and Biological Sciences Research Council (BB/J018236/1) and Kidney Research UK. E.R.C. is supported as an Investigator of the Howard Hughes Medical Institute.
dc.languageEnglishen
dc.language.isoenen
dc.publisherNPG
dc.titleExocytotic fusion pores are composed of both lipids and proteinsen
dc.typeArticle
dc.description.versionThis is the author accepted manuscript. The final version is available from NPG via http://dx.doi.org/10.1038/nsmb.3141en
prism.endingPage73
prism.publicationDate2015en
prism.publicationNameNature Structural and Molecular Biologyen
prism.startingPage67
prism.volume23en
dc.rioxxterms.funderNIH
dc.rioxxterms.funderBBSRC
dc.rioxxterms.projectidMH061876
dc.rioxxterms.projectidBB/J018236/1
dcterms.dateAccepted2015-11-13en
rioxxterms.versionofrecord10.1038/nsmb.3141en
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2015-12-14en
dc.identifier.eissn1545-9985
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idBBSRC (BB/J018236/1)
rioxxterms.freetoread.startdate2016-06-14


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