Evidence map›Paper›PMID 24957337›Full record

ArticleeLife2014

Molecular mechanism for Rabex-5 GEF activation by Rabaptin-5.

Zhe Zhang, Tianlong Zhang, Shanshan Wang, Zhou Gong, Chun Tang, Jiangye Chen, Jianping Ding

Open access · goldAbstract read
In one paragraph

Article in eLife, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
3.5field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

37 citing papers in PubMed, 73 citations in OpenAlex.

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  5. ESCRTing the RABs through conversion.Biochemical Society transactions · 2025
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  10. Structural basis for Rab6 activation by the Ric1-Rgp1 complex.bioRxiv : the preprint server for biology · 2024
    Article
  11. Article
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  13. Article
  14. Article
  15. Poly(ADP-ribose) Polymerase 1 Mediates Rab5 Inactivation after DNA Damage.International journal of molecular sciences · 2022
    Article
  16. Article
  17. Article
  18. Article
  19. Review
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 4 institutions in 2 countries.

Zhe ZhangState Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
Tianlong ZhangState Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
Shanshan WangState Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
Zhou GongState Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan, China.
Chun TangState Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan, China.
Jiangye ChenState Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
Jianping DingState Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
Chinese Academy of Sciences · CNMRC Laboratory of Molecular Biology · GBShanghai Institutes for Biological Sciences · CNWuhan Institute of Physics and Mathematics · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Rabex-5 and Rabaptin-5 function together to activate Rab5 and further promote early endosomal fusion in endocytosis. The Rabex-5 GEF activity is autoinhibited by the Rabex-5 CC domain (Rabex-5CC) and activated by the Rabaptin-5 C2-1 domain (Rabaptin-5C21) with yet unknown mechanism. We report here the crystal structures of Rabex-5 in complex with the dimeric Rabaptin-5C21 (Rabaptin-5C212) and in complex with Rabaptin-5C212 and Rab5, along with biophysical and biochemical analyses. We show that Rabex-5CC assumes an amphipathic α-helix which binds weakly to the substrate-binding site of the GEF domain, leading to weak autoinhibition of the GEF activity. Binding of Rabaptin-5C21 to Rabex-5 displaces Rabex-5CC to yield a largely exposed substrate-binding site, leading to release of the GEF activity. In the ternary complex the substrate-binding site of Rabex-5 is completely exposed to bind and activate Rab5. Our results reveal the molecular mechanism for the regulation of the Rabex-5 GEF activity.

Indexed as

EndocytosisBinding SitesBiophysicsCrystallography, X-RayGlutathione TransferaseGuanine Nucleotide Exchange FactorsHumansProtein BindingProtein Structure, TertiaryScattering, Small AngleTrypsinVesicular Transport ProteinsX-Ray DiffractionGlutathione TransferaseGuanine Nucleotide Exchange FactorsRABEP1 protein, humanRABGEF1 protein, humanTrypsinVesicular Transport Proteinsbiochemistrybiophysicscrystal structureE. coliGEF activityhumanmolecular mechanismRab5Rabaptin-5rabex-5structural biology

Identifiers

PMID24957337
PMCPMC4102244
OpenAlexW2133059094

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Registered trials

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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.