1. Structure of the Mon1-Ccz1 complex reveals molecular basis of membrane binding for Rab7 activation.
- Author
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Klink BU, Herrmann E, Antoni C, Langemeyer L, Kiontke S, Gatsogiannis C, Ungermann C, Raunser S, and Kümmel D
- Subjects
- Cell Membrane genetics, Chaetomium genetics, Fungal Proteins genetics, Multiprotein Complexes genetics, rab7 GTP-Binding Proteins genetics, Cell Membrane metabolism, Chaetomium metabolism, Fungal Proteins metabolism, Multiprotein Complexes metabolism, rab7 GTP-Binding Proteins metabolism
- Abstract
Activation of the GTPase Rab7/Ypt7 by its cognate guanine nucleotide exchange factor (GEF) Mon1-Ccz1 marks organelles such as endosomes and autophagosomes for fusion with lysosomes/vacuoles and degradation of their content. Here, we present a high-resolution cryogenic electron microscopy structure of the Mon1-Ccz1 complex that reveals its architecture in atomic detail. Mon1 and Ccz1 are arranged side by side in a pseudo-twofold symmetrical heterodimer. The three Longin domains of each Mon1 and Ccz1 are triangularly arranged, providing a strong scaffold for the catalytic center of the GEF. At the opposite side of the Ypt7-binding site, a positively charged and relatively flat patch stretches the Longin domains 2/3 of Mon1 and functions as a phosphatidylinositol phosphate-binding site, explaining how the GEF is targeted to membranes. Our work provides molecular insight into the mechanisms of endosomal Rab activation and serves as a blueprint for understanding the function of members of the Tri Longin domain Rab-GEF family., Competing Interests: The authors declare no competing interest., (Copyright © 2022 the Author(s). Published by PNAS.)
- Published
- 2022
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