Architecture and mechanism of the late endosomal Rab7-like Ypt7 guanine nucleotide exchange factor complex Mon1–Ccz1
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https://osnadocs.ub.uni-osnabrueck.de/handle/urn:nbn:de:gbv:700-2018043016920
https://osnadocs.ub.uni-osnabrueck.de/handle/urn:nbn:de:gbv:700-2018043016920
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 |
URL: | https://osnadocs.ub.uni-osnabrueck.de/handle/urn:nbn:de:gbv:700-2018043016920 |
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: | http://creativecommons.org/licenses/by/4.0/ |
Type of publication: | Einzelbeitrag in einer wissenschaftlichen Zeitschrift [article] |
Appears in Collections: | FB05 - Hochschulschriften Open-Access-Publikationsfonds |
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File | Description | Size | Format | |
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ncomms_8_14034_2017_Kuemmel.pdf | 1,48 MB | Adobe PDF | ncomms_8_14034_2017_Kuemmel.pdf View/Open |
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