Structure of the metazoan Rab7 GEF complex Mon1–Ccz1–Bulli

DC FieldValueLanguage
dc.contributor.authorHerrmann, Eric
dc.contributor.authorSchäfer, Jan-Hannes
dc.contributor.authorWilmes, Stephan
dc.contributor.authorUngermann, Christian
dc.contributor.authorMoeller, Arne
dc.contributor.authorKümmel, Daniel
dc.date.accessioned2023-07-12T06:59:24Z-
dc.date.available2023-07-12T06:59:24Z-
dc.date.issued2023
dc.identifier.issn0027-8424
dc.identifier.urihttp://osnascholar.ub.uni-osnabrueck.de/handle/unios/72064-
dc.descriptionCited by: 0; All Open Access, Green Open Access, Hybrid Gold Open Access
dc.description.abstractThe endosomal system of eukaryotic cells represents a central sorting and recycling compartment linked to metabolic signaling and the regulation of cell growth. Tightly controlled activation of Rab GTPases is required to establish the different domains of endosomes and lysosomes. In metazoans, Rab7 controls endosomal maturation, autophagy, and lysosomal function. It is activated by the guanine nucleotide exchange factor (GEF) complex Mon1–Ccz1–Bulli (MCBulli) of the tri-longin domain (TLD) family. While the Mon1 and Ccz1 subunits have been shown to constitute the active site of the complex, the role of Bulli remains elusive. We here present the cryo-electron microscopy (cryo-EM) structure of MCBulli at 3.2 Å resolution. Bulli associates as a leg-like extension at the periphery of the Mon1 and Ccz1 heterodimers, consistent with earlier reports that Bulli does not impact the activity of the complex or the interactions with recruiter and substrate GTPases. While MCBulli shows structural homology to the related ciliogenesis and planar cell polarity effector (Fuzzy–Inturned–Wdpcp) complex, the interaction of the TLD core subunits Mon1-Ccz1 and Fuzzy–Inturned with Bulli and Wdpcp, respectively, is remarkably different. The variations in the overall architecture suggest divergent functions of the Bulli and Wdpcp subunits. Based on our structural analysis, Bulli likely serves as a recruitment platform for additional regulators of endolysosomal trafficking to sites of Rab7 activation. Copyright © 2023 the Author(s). Published by PNAS. This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY).
dc.language.isoen
dc.publisherNational Academy of Sciences
dc.relation.ispartofProceedings of the National Academy of Sciences of the United States of America
dc.subjectAnimals
dc.subjectCryoelectron Microscopy
dc.subjectEndosomes
dc.subjectGuanine Nucleotide Exchange Factors
dc.subjectProtein Transport
dc.subjectrab GTP-Binding Proteins
dc.subjectVesicular Transport Proteins
dc.subjectguanine nucleotide exchange factor
dc.subjectRab protein
dc.subjectvesicular transport protein
dc.subjectanimal
dc.subjectcryoelectron microscopy
dc.subjectendosome
dc.subjectmetabolism
dc.subjectprotein transport
dc.titleStructure of the metazoan Rab7 GEF complex Mon1–Ccz1–Bulli
dc.typejournal article
dc.identifier.doi10.1073/pnas.2301908120
dc.identifier.scopus2-s2.0-85158107408
dc.identifier.urlhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85158107408&doi=10.1073%2fpnas.2301908120&partnerID=40&md5=0033aebd0b4023fa1afb0f2ef67dd8fc
dc.description.volume120
dc.description.issue20
dcterms.isPartOf.abbreviationProc. Natl. Acad. Sci. U. S. A.
local.import.remainsaffiliations : Department of Chemistry and Pharmacy, Institute of Biochemistry, University of Münster, Münster, 48149, Germany; Department of Biology/ Chemistry, Structural Biology section, Osnabrück University, Osnabrück, 49076, Germany; Department of Biology/Chemistry, Biochemistry section, Osnabrück University, Osnabrück, 49076, Germany; Center of Cellular Nanoanalytic Osnabrück, Osnabrück University, Osnabrück, 49076, Germany
local.import.remainscorrespondence_address : A. Moeller; Department of Biology/ Chemistry, Structural Biology section, Osnabrück University, Osnabrück, 49076, Germany; email: arne.moeller@uni-osnabrueck.de; D. Kümmel; Department of Chemistry and Pharmacy, Institute of Biochemistry, University of Münster, Münster, 48149, Germany; email: daniel.kuemmel@uni-muenster.de
local.import.remainspmid : 37155863
local.import.remainspublication_stage : Final
crisitem.author.deptFB 05 - Biologie/Chemie-
crisitem.author.deptFB 05 - Biologie/Chemie-
crisitem.author.deptidfb05-
crisitem.author.deptidfb05-
crisitem.author.parentorgUniversität Osnabrück-
crisitem.author.parentorgUniversität Osnabrück-
crisitem.author.netidUnCh999-
crisitem.author.netidMoAr687-
crisitem.author.netidKuDa343-
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