Structure of the HOPS tethering complex, a lysosomal membrane fusion machinery

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dc.contributor.authorShvarev, Dmitry
dc.contributor.authorSchoppe, Jannis
dc.contributor.authorKoenig, Caroline
dc.contributor.authorPerz, Angela
dc.contributor.authorFuellbrunn, Nadia
dc.contributor.authorKiontke, Stephan
dc.contributor.authorLangemeyer, Lars
dc.contributor.authorJanuliene, Dovile
dc.contributor.authorSchnelle, Kilian
dc.contributor.authorKuemmel, Daniel
dc.contributor.authorFroehlich, Florian
dc.contributor.authorMoeller, Arne
dc.contributor.authorUngermann, Christian
dc.date.accessioned2023-02-17T11:35:14Z-
dc.date.available2023-02-17T11:35:14Z-
dc.date.issued2022
dc.identifier.issn2050-084X
dc.identifier.urihttp://osnascholar.ub.uni-osnabrueck.de/handle/unios/65491-
dc.description.abstractLysosomes are essential for cellular recycling, nutrient signaling, autophagy, and pathogenic bacteria and viruses invasion. Lysosomal fusion is fundamental to cell survival and requires HOPS, a conserved heterohexameric tethering complex. On the membranes to be fused, HOPS binds small membrane-associated GTPases and assembles SNAREs for fusion, but how the complex fulfills its function remained speculative. Here, we used cryo-electron microscopy to reveal the structure of HOPS. Unlike previously reported, significant flexibility of HOPS is confined to its extremities, where GTPase binding occurs. The SNARE-binding module is firmly attached to the core, therefore, ideally positioned between the membranes to catalyze fusion. Our data suggest a model for how HOPS fulfills its dual functionality of tethering and fusion and indicate why it is an essential part of the membrane fusion machinery.
dc.description.sponsorshipDeutsche Forschungsgemeinschaft [UN111/5-6, INST190/196-1 FUGG, SFB 944 P11, SFB 944 P27, SFB 944 P20, SFB 944 P16, MO 2752/3-6]; Bundesministerium fuer Bildung und Forschung [BMBF/DLR 01ED2010]; Deutsche Forschungsgemeinschaft UN111/5-6 Christian UngermannDeutsche Forschungsgemeinschaft INST190/196-1 FUGG Arne MoellerBundesministerium fuer Bildung und Forschung BMBF/DLR 01ED2010 Arne MoellerDeutsche Forschungsgemeinschaft SFB 944 P11 Christian UngermannDeutsche Forschungsgemeinschaft SFB 944 P27 Arne MoellerDeutsche Forschungsgemeinschaft SFB 944 P20 Florian FroehlichDeutsche Forschungsgemeinschaft SFB 944 P16 Daniel KuemmelDeutsche Forschungsgemeinschaft MO 2752/3-6 Arne MoellerThe funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
dc.language.isoen
dc.publishereLIFE SCIENCES PUBL LTD
dc.relation.ispartofELIFE
dc.subjectBiology
dc.subjectcerevisiae
dc.subjectCORVET
dc.subjectCRYO-EM
dc.subjectFINGER PROTEIN
dc.subjectHIGH-ACCURACY
dc.subjectHOPS
dc.subjectLife Sciences & Biomedicine - Other Topics
dc.subjectlysosome
dc.subjectmembrane fusion
dc.subjectMOLECULAR ARCHITECTURE
dc.subjectMULTIPLE SEQUENCE ALIGNMENT
dc.subjectRab GTPase
dc.subjectRAB INTERACTIONS
dc.subjectREQUIRES
dc.subjectS
dc.subjectSNARE COMPLEX
dc.subjecttethering
dc.subjectvacuole
dc.subjectVACUOLE FUSION
dc.titleStructure of the HOPS tethering complex, a lysosomal membrane fusion machinery
dc.typejournal article
dc.identifier.doi10.7554/eLife.80901
dc.identifier.isiISI:000875937600001
dc.description.volume11
dc.contributor.orcid0000-0002-4309-0910
dc.contributor.orcid0000-0002-3279-7590
dc.contributor.orcid0000-0002-9776-268X
dc.contributor.orcid0000-0002-0767-9031
dc.contributor.orcid0000-0001-8808-594X
dc.contributor.orcid0000-0003-3950-5914
dc.publisher.placeSHERATON HOUSE, CASTLE PARK, CAMBRIDGE, CB3 0AX, ENGLAND
dcterms.isPartOf.abbreviationeLife
dcterms.oaStatusgold, Green Submitted, Green Published
local.import.remainsaffiliations : University Osnabruck; University Osnabruck; Philipps University Marburg; University of Munster; University Osnabruck; University Osnabruck
local.import.remainsweb-of-science-index : Science Citation Index Expanded (SCI-EXPANDED)
crisitem.author.deptFB 05 - Biologie/Chemie-
crisitem.author.deptFB 05 - Biologie/Chemie-
crisitem.author.deptSonderforschungsbereich 944: Physiologie und Dynamik zellulärer Mikrokompartimente-
crisitem.author.deptFB 05 - Biologie/Chemie-
crisitem.author.deptidfb05-
crisitem.author.deptidfb05-
crisitem.author.deptidorganisation19-
crisitem.author.deptidfb05-
crisitem.author.orcid0000-0002-3279-7590-
crisitem.author.orcid0000-0001-8307-2189-
crisitem.author.parentorgUniversität Osnabrück-
crisitem.author.parentorgUniversität Osnabrück-
crisitem.author.parentorgFB 05 - Biologie/Chemie-
crisitem.author.parentorgUniversität Osnabrück-
crisitem.author.grandparentorgUniversität Osnabrück-
crisitem.author.netidJaDo206-
crisitem.author.netidKuDa343-
crisitem.author.netidFrFl166-
crisitem.author.netidMoAr687-
crisitem.author.netidUnCh999-
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