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

Please use this identifier to cite or link to this item:
Open Access logo originally created by the Public Library of Science (PLoS)
Title: Architecture and mechanism of the late endosomal Rab7-like Ypt7 guanine nucleotide exchange factor complex Mon1–Ccz1
Authors: Kiontke, Stephan
Langemeyer, Lars
Kuhlee, Anne
Schuback, Saskia
Raunser, Stefan
Ungermann, Christian
Kümmel, Daniel
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.
Citations: Nature Communications 8, Article number: 14034, 2017
Subject Keywords: Endosome; MC1; Guanine nucleotide exchange factor; Rab GTPase; Ypt7; Rab7
Issue Date: 30-Apr-2018
License name: Namensnennung 4.0 International
License url:
Type of publication: Einzelbeitrag in einer wissenschaftlichen Zeitschrift [article]
Appears in Collections:FB05 - Hochschulschriften

Files in This Item:
File Description SizeFormat 
ncomms_8_14034_2017_Kuemmel.pdf1,48 MBAdobe PDF

This item is licensed under a Creative Commons License Creative Commons