ArticleProceedings of the National Academy of Sciences of the United States of America2023
Structure of the metazoan Rab7 GEF complex Mon1-Ccz1-Bulli.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed, 18 citations in OpenAlex.
- Endosomal maturation is controlled by the trimeric Bulli-Mon1-Ccz1 Rab7 GEF complex and the Rab5 GTPase-activating protein GAPsec.Journal of cell science · 2026Article
- Identification of conserved residues essential for the ciliogenic functions of WDPCP.Disease models & mechanisms · 2025Article
- Cryo-EM structure of the human MON1A-CCZ1-RAB7A complex provides insights into nucleotide exchange mechanism.Life metabolism · 2025Article
- Structural insights into RAB7A activation: a mammalian perspective on the MON1A-CCZ1 GEF complex.Life metabolism · 2025Article
- Mechanistic adaptation of the metazoan RabGEFs Mon1-Ccz1 and Fuzzy-Inturned.Science advances · 2025Article
- Mechanistic insights into the GEF activity of the human MON1A/CCZ1/C18orf8 complex.Protein & cell · 2025Article
- The human ciliopathy protein RSG1 links the CPLANE complex to transition zone architecture.Nature communications · 2025Article
- ESCRTing the RABs through conversion.Biochemical Society transactions · 2025Review
- Cryo-EM structure of the BLOC-3 complex provides insights into the pathogenesis of Hermansky-Pudlak syndrome.Nature communications · 2025Article
- Targeting secretory autophagy in solid cancers: mechanisms, immune regulation and clinical insights.Experimental hematology & oncology · 2025Review
- Structural basis for Rab6 activation by the Ric1-Rgp1 complex.Nature communications · 2024Article
- Evolutionary origins of the lysosome-related organelle sorting machinery reveal ancient homology in post-endosome trafficking pathways.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Structural basis for Rab6 activation by the Ric1-Rgp1 complex.bioRxiv : the preprint server for biology · 2024Article
- Molecular structures and function of the autophagosome-lysosome fusion machinery.Autophagy reports · 2024Article
- Regulatory sites in the Mon1-Ccz1 complex control Rab5 to Rab7 transition and endosome maturation.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
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.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.