Architecture and mechanism of the late endosomal Rab7-like Ypt7 guanine nucleotide exchange factor complex Mon1-Ccz1

DC FieldValueLanguage
dc.contributor.authorKiontke, Stephan
dc.contributor.authorLangemeyer, Lars
dc.contributor.authorKuhlee, Anne
dc.contributor.authorSchuback, Saskia
dc.contributor.authorRaunser, Stefan
dc.contributor.authorUngermann, Christian
dc.contributor.authorKuemmel, Daniel
dc.date.accessioned2021-12-23T16:07:15Z-
dc.date.available2021-12-23T16:07:15Z-
dc.date.issued2017
dc.identifier.issn20411723
dc.identifier.urihttps://osnascholar.ub.uni-osnabrueck.de/handle/unios/7785-
dc.description.abstractThe Mon1-Ccz1 complex (MC1) is the guanine nucleotide exchange factor (GEF) for the Rab GTPase Ypt7/Rab7 and is required for endosomal maturation and fusion at the vacuole/lysosome. Here we present the overall architecture of MC1 from Chaetomium thermophilum, and in combining biochemical studies and mutational analysis in yeast, we identify the domains required for catalytic activity, complex assembly and localization of MC1. The crystal structure of a catalytic MC1 core complex bound to Ypt7 provides mechanistic insight into its function. We pinpoint the determinants that allow for a discrimination of the Rab7-like Ypt7 over the Rab5-like Vps21, which are both located on the same membrane. MC1 shares structural similarities with the TRAPP complex, but employs a novel mechanism to promote nucleotide exchange that utilizes a conserved lysine residue of Ypt7, which is inserted upon MC1 binding into the nucleotide-binding pocket of Ypt7 and contributes to specificity.
dc.description.sponsorshipDFGGerman Research Foundation (DFG)European Commission [KU2531/2-1, SFB 944-P17, SFB944-P11, RA 1781/2-3]; Department of Biology/Chemistry in Osnabruck; We acknowledge the Helmholtz-Zentrum Berlin for provision of synchrotron radiation beamtime at beamline MX14.1 & MX14.3 of BESSY II and would like to thank Uwe Muller for assistance. We are grateful to Johanna Kallio, Michele Cianci and the staff of the EMBL beamline P13 at the PETRA III synchrotron for excellent support during data collection and Siegfried Engelbrecht-Vandre for helpful discussions. We are grateful to Eric Herrmann for technical assistance. L.L. was supported in part by an incentive award of the Department of Biology/Chemistry in Osnabruck. This study was supported by grants from DFG to D.K. (KU2531/2-1, SFB 944-P17), C.U. (SFB944-P11) and S.R. (RA 1781/2-3).
dc.language.isoen
dc.publisherNATURE PUBLISHING GROUP
dc.relation.ispartofNATURE COMMUNICATIONS
dc.subjectACTIVATION
dc.subjectCRYSTAL-STRUCTURE
dc.subjectHERMANSKY-PUDLAK SYNDROME
dc.subjectIDENTIFICATION
dc.subjectMultidisciplinary Sciences
dc.subjectPHENIX
dc.subjectPROTEIN COMPLEX
dc.subjectRAB7 GTPASE
dc.subjectScience & Technology - Other Topics
dc.subjectSTRUCTURAL BASIS
dc.subjectSTRUCTURE REFINEMENT
dc.subjectVACUOLE
dc.titleArchitecture and mechanism of the late endosomal Rab7-like Ypt7 guanine nucleotide exchange factor complex Mon1-Ccz1
dc.typejournal article
dc.identifier.doi10.1038/ncomms14034
dc.identifier.isiISI:000391195400001
dc.description.volume8
dc.contributor.orcid0000-0002-4309-0910
dc.contributor.orcid0000-0001-9373-3016
dc.publisher.placeMACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
dcterms.isPartOf.abbreviationNat. Commun.
dcterms.oaStatusGreen Published, gold, Green Submitted
crisitem.author.deptFB 05 - Biologie/Chemie-
crisitem.author.deptidfb05-
crisitem.author.parentorgUniversität Osnabrück-
crisitem.author.netidUnCh999-
crisitem.author.netidKuDa343-
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