ArticleeLife2019
Auto-regulation of Rab5 GEF activity in Rabex5 by allosteric structural changes, catalytic core dynamics and ubiquitin binding.
Article in eLife, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
19 citing papers in PubMed, 49 citations in OpenAlex.
- Article
- Lipid turnover and GEF recruitment collectively determine Rab5 recruitment and activation during the first step of early endosome formation.Nature communications · 2026Article
- RABEP1 regulates neutrophil migration via endosomal recycling and actin polymerization.Journal of leukocyte biology · 2026Article
- Article
- RABEP1 amplifies front signaling in neutrophil migration.bioRxiv : the preprint server for biology · 2025Article
- ESCRTing the RABs through conversion.Biochemical Society transactions · 2025Review
- Biochemical and structural characterization of Rab3GAP reveals insights into Rab18 nucleotide exchange activity.Nature communications · 2025Article
- Spatiotemporal recruitment of the ubiquitin-specific protease USP8 directs endosome maturation.eLife · 2024Article
- Loss of HD-PTP function results in lipodystrophy, defective cellular signaling and altered lipid homeostasis.Journal of cell science · 2024Article
- Sec7 regulatory domains scaffold autoinhibited and active conformations.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Rabex-5 E3 and Rab5 GEF domains differ in their regulation of Ras, Notch, and PI3K signaling in Drosophila wing development.PloS one · 2024Article
- Structural basis for activation of Arf1 at the Golgi complex.Cell reports · 2022Article
- PI Kinase-EhGEF2-EhRho5 axis contributes to LPA stimulated macropinocytosis in Entamoeba histolytica.PLoS pathogens · 2022Article
- Down Syndrome Fetal Fibroblasts Display Alterations of Endosomal Trafficking Possibly due to SYNJ1 Overexpression.Frontiers in genetics · 2022Article
- Activation Mechanisms of the VPS34 Complexes.Cells · 2021Review
- His domain protein tyrosine phosphatase and Rabaptin-5 couple endo-lysosomal sorting of EGFR with endosomal maturation.Journal of cell science · 2021Article
- Small GTPases of the Rab and Arf Families: Key Regulators of Intracellular Trafficking in Neurodegeneration.International journal of molecular sciences · 2021Review
- Article
- Stochastic activation and bistability in a Rab GTPase regulatory network.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
Corrections and comments
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Authors and funding
13 authors at 7 institutions in 2 countries.
Funding
Abstract
Intracellular trafficking depends on the function of Rab GTPases, whose activation is regulated by guanine exchange factors (GEFs). The Rab5 GEF, Rabex5, was previously proposed to be auto-inhibited by its C-terminus. Here, we studied full-length Rabex5 and Rabaptin5 proteins as well as domain deletion Rabex5 mutants using hydrogen deuterium exchange mass spectrometry. We generated a structural model of Rabex5, using chemical cross-linking mass spectrometry and integrative modeling techniques. By correlating structural changes with nucleotide exchange activity for each construct, we uncovered new auto-regulatory roles for the ubiquitin binding domains and the Linker connecting those domains to the catalytic core of Rabex5. We further provide evidence that enhanced dynamics in the catalytic core are linked to catalysis. Our results suggest a more complex auto-regulation mechanism than previously thought and imply that ubiquitin binding serves not only to position Rabex5 but to also control its Rab5 GEF activity through allosteric structural alterations.
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Registered trials
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.