8c7g | pdb_00008c7g

Drosophila melanogaster Rab7 GEF complex Mon1-Ccz1-Bulli

spinqualitylabelsall models 8c7g, resolution 3.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8c7g is a 3 chain structure with sequence from Drosophila melanogaster. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.2Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function RMC1_DROME Positive regulator of the Rab7 guanyl-nucleotide exchange activity of the Mon1-Ccz1 complex, possibly by enhancing its endosomal membrane association (PubMed:32391792, PubMed:32499409). As part of the Mon1-Ccz1 complex involved in endolysosomal biogenesis possibly by mediating Rab conversion, the replacement of Rab5 with Rab7 during late endosome maturation (PubMed:32499409). Publication Abstract from PubMed 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 A 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. Structure of the metazoan Rab7 GEF complex Mon1-Ccz1-Bulli.,Herrmann E, Schafer JH, Wilmes S, Ungermann C, Moeller A, Kummel D Proc Natl Acad Sci U S A. 2023 May 16;120(20):e2301908120. doi: , 10.1073/pnas.2301908120. Epub 2023 May 8. PMID:37155863 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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