ArticlePLoS biology2013
Integrated conformational and lipid-sensing regulation of endosomal ArfGEF BRAG2.
Article in PLoS biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 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.
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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
35 citing papers in PubMed, 49 citations in OpenAlex.
- Putting a lid on it: The N-terminal helix of Arf1 inhibits switching via uniform stabilization.Biophysical journal · 2025Article
- A molten globule ensemble primes Arf1-GDP for the nucleotide switch.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Analysis of Protein Cysteine Acylation Using a Modified Suspension Trap (Acyl-Trap).Journal of proteome research · 2024Article
- Analysis of Protein Cysteine Acylation Using a Modified Suspension Trap (Acyl-Trap).bioRxiv : the preprint server for biology · 2024Article
- The Abl-interactor Abi suppresses the function of the BRAG2 GEF family member Schizo.Biology open · 2024Article
- Preliminary Study on Clinical Characteristics and Pathogenesis ofPharmacogenomics and personalized medicine · 2024Article
- Article
- Ca2+-induced release of IQSEC2/BRAG1 autoinhibition under physiological and pathological conditions.The Journal of cell biology · 2023Article
- Arf6 as a therapeutic target: Structure, mechanism, and inhibitors.Acta pharmaceutica Sinica. B · 2023Review
- Membranes prime the RapGEF EPAC1 to transduce cAMP signaling.Nature communications · 2023Article
- Structural basis for activation of Arf1 at the Golgi complex.Cell reports · 2022Article
- IQSEC2-related encephalopathy in males due to missense variants in the pleckstrin homology domain.Clinical genetics · 2022Article
- Structural basis for the initiation of COPII vesicle biogenesis.Structure (London, England : 1993) · 2021Article
- Revealing the activation mechanism of autoinhibited RalF by integrated simulation and experimental approaches.Scientific reports · 2021Article
- Article
- Structural Organization and Dynamics of Homodimeric Cytohesin Family Arf GTPase Exchange Factors in Solution and on Membranes.Structure (London, England : 1993) · 2019Article
- Interaction of the N terminus of ADP-ribosylation factor with the PH domain of the GTPase-activating protein ASAP1 requires phosphatidylinositol 4,5-bisphosphate.The Journal of biological chemistry · 2019Article
- ARF GTPases and their GEFs and GAPs: concepts and challenges.Molecular biology of the cell · 2019Review
- PH-domain-binding inhibitors of nucleotide exchange factor BRAG2 disrupt Arf GTPase signaling.Nature chemical biology · 2019Article
- Structural Dynamics Control Allosteric Activation of Cytohesin Family Arf GTPase Exchange Factors.Structure (London, England : 1993) · 2018Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The mechanisms whereby guanine nucleotide exchange factors (GEFs) coordinate their subcellular targeting to their activation of small GTPases remain poorly understood. Here we analyzed how membranes control the efficiency of human BRAG2, an ArfGEF involved in receptor endocytosis, Wnt signaling, and tumor invasion. The crystal structure of an Arf1-BRAG2 complex that mimics a membrane-bound intermediate revealed an atypical PH domain that is constitutively anchored to the catalytic Sec7 domain and interacts with Arf. Combined with the quantitative analysis of BRAG2 exchange activity reconstituted on membranes, we find that this PH domain potentiates nucleotide exchange by about 2,000-fold by cumulative conformational and membrane-targeting contributions. Furthermore, it restricts BRAG2 activity to negatively charged membranes without phosphoinositide specificity, using a positively charged surface peripheral to but excluding the canonical lipid-binding pocket. This suggests a model of BRAG2 regulation along the early endosomal pathway that expands the repertoire of GEF regulatory mechanisms. Notably, it departs from the auto-inhibitory and feedback loop paradigm emerging from studies of SOS and cytohesins. It also uncovers a novel mechanism of unspecific lipid-sensing by PH domains that may allow sustained binding to maturating membranes.
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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.