8C7G

Drosophila melanogaster Rab7 GEF complex Mon1-Ccz1-Bulli

8C7G の概要

• エントリーDOI: 10.2210/pdb8c7g/pdb
• EMDBエントリー: 16457 16462 16463 16464
• 分子名称: Mic1 domain-containing protein, Caffeine, calcium, zinc sensitivity 1, Vacuolar fusion protein MON1 homolog (3 entities in total)
• 機能のキーワード: guanain nucleotide exchange factor, membrane traffic, lysosome, endocytosis
• 由来する生物種: Drosophila melanogaster (fruit fly); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 190271.11

構造登録者

Schaefer, J.,Herrmann, E.,Kuemmel, D.,Moeller, A. (登録日: 2023-01-15, 公開日: 2023-05-17, 最終更新日: 2024-07-24)

主引用文献

Herrmann, E.,Schafer, J.H.,Wilmes, S.,Ungermann, C.,Moeller, A.,Kummel, D.
Structure of the metazoan Rab7 GEF complex Mon1-Ccz1-Bulli.
Proc.Natl.Acad.Sci.USA, 120:e2301908120-e2301908120, 2023

PubMed Abstract: The endosomal system of eukaryotic cells represents a central sorting and recycling compartment linked to metabolic signaling and the regulation of cell growth. Tightly controlled activation of Rab GTPases is required to establish the different domains of endosomes and lysosomes. In metazoans, Rab7 controls endosomal maturation, autophagy, and lysosomal function. It is activated by the guanine nucleotide exchange factor (GEF) complex Mon1-Ccz1-Bulli (MCBulli) of the tri-longin domain (TLD) family. While the Mon1 and Ccz1 subunits have been shown to constitute the active site of the complex, the role of Bulli remains elusive. We here present the cryo-electron microscopy (cryo-EM) structure of MCBulli at 3.2 Å resolution. Bulli associates as a leg-like extension at the periphery of the Mon1 and Ccz1 heterodimers, consistent with earlier reports that Bulli does not impact the activity of the complex or the interactions with recruiter and substrate GTPases. While MCBulli shows structural homology to the related ciliogenesis and planar cell polarity effector (Fuzzy-Inturned-Wdpcp) complex, the interaction of the TLD core subunits Mon1-Ccz1 and Fuzzy-Inturned with Bulli and Wdpcp, respectively, is remarkably different. The variations in the overall architecture suggest divergent functions of the Bulli and Wdpcp subunits. Based on our structural analysis, Bulli likely serves as a recruitment platform for additional regulators of endolysosomal trafficking to sites of Rab7 activation.

PubMed: 37155863
DOI: 10.1073/pnas.2301908120

実験手法

ELECTRON MICROSCOPY (3.2 Å)