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-Structure paper
タイトル | Structure of the Mon1-Ccz1 complex reveals molecular basis of membrane binding for Rab7 activation. |
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ジャーナル・号・ページ | Proc Natl Acad Sci U S A, Vol. 119, Issue 6, Year 2022 |
掲載日 | 2022年2月8日 |
著者 | Björn U Klink / Eric Herrmann / Claudia Antoni / Lars Langemeyer / Stephan Kiontke / Christos Gatsogiannis / Christian Ungermann / Stefan Raunser / Daniel Kümmel / |
PubMed 要旨 | 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 ...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. |
リンク | Proc Natl Acad Sci U S A / PubMed:35105815 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.85 Å |
構造データ | EMDB-14066, PDB-7qla: |
由来 |
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キーワード | ENDOCYTOSIS / guanine nucleotide exchange factor / TLD Rab GEF / longin domains / PIP binding |