title: Architecture and mechanism of the late endosomal Rab7-like Ypt7 guanine nucleotide exchange factor complex Mon1-Ccz1.
abstract: The 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.
authors.affiliation: Division of Structural Biology, Department of Biology/Chemistry, University of Osnabrück, Barbarastraße 13, Osnabrück 49076, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Kiontke
authors.affiliation: Biochemistry Section, Department of Biology/Chemistry, University of Osnabrück, Barbarastraße 13, Osnabrück 49076, Germany.
authors.forename: Lars
authors.initials: L
authors.lastname: Langemeyer
authors.affiliation: Department of Structural Biochemistry, Max-Planck-Institute of Molecular Physiology, Otto-Hahn-Straße 11, Dortmund 44227, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Kuhlee
authors.affiliation: Division of Structural Biology, Department of Biology/Chemistry, University of Osnabrück, Barbarastraße 13, Osnabrück 49076, Germany.
authors.forename: Saskia
authors.initials: S
authors.lastname: Schuback
authors.affiliation: Department of Structural Biochemistry, Max-Planck-Institute of Molecular Physiology, Otto-Hahn-Straße 11, Dortmund 44227, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Raunser
authors.affiliation: Biochemistry Section, Department of Biology/Chemistry, University of Osnabrück, Barbarastraße 13, Osnabrück 49076, Germany.
authors.forename: Christian
authors.identifier: 0000-0003-4331-8695
authors.initials: C
authors.lastname: Ungermann
authors.affiliation: Division of Structural Biology, Department of Biology/Chemistry, University of Osnabrück, Barbarastraße 13, Osnabrück 49076, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Kümmel
mesh_terms: D002597:Chaetomium / Q000502:physiology*; D018360:Crystallography, X-Ray; D011992:Endosomes / Q000378:metabolism; D005656:Fungal Proteins / Q000737:chemistry* / Q000502:physiology; D020662:Guanine Nucleotide Exchange Factors / Q000737:chemistry* / Q000502:physiology; D008247:Lysosomes / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology; D000072417:Protein Domains / Q000502:physiology; D055503:Protein Multimerization / Q000502:physiology; D021381:Protein Transport / Q000502:physiology; D013379:Substrate Specificity / Q000502:physiology; D014617:Vacuoles / Q000378:metabolism; D033921:Vesicular Transport Proteins / Q000737:chemistry* / Q000502:physiology; D020691:rab GTP-Binding Proteins / Q000737:chemistry* / Q000502:physiology
chemical_list: D005656:Fungal Proteins; D020662:Guanine Nucleotide Exchange Factors; D033921:Vesicular Transport Proteins; D020691:rab GTP-Binding Proteins