ArticleNature structural & molecular biology2008
Internal dynamics control activation and activity of the autoinhibited Vav DH domain.
Article in Nature structural & molecular biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 100 citations in OpenAlex.
- Structure-based drug repurposing and in vitro evaluation of VAV2-associated candidates for suppression of macrophage foam-cell formation in atherosclerosis.Molecular diversity · 2026Article
- Challenging AlphaFold in predicting proteins with large-scale allosteric transitions.Communications chemistry · 2025Article
- The fitness cost of spurious phosphorylation.The EMBO journal · 2024Article
- Autoinhibited Protein Database: a curated database of autoinhibitory domains and their autoinhibition mechanisms.Database : the journal of biological databases and curation · 2024Article
- The fitness cost of spurious phosphorylation.bioRxiv : the preprint server for biology · 2023Article
- Transient exposure of a buried phosphorylation site in an autoinhibited protein.Biophysical journal · 2022Article
- A Tale of Two Tyrosines.Biophysical journal · 2020Article
- Protein Dynamics Enables Phosphorylation of Buried Residues in Cdk2/Cyclin-A-Bound p27.Biophysical journal · 2020Article
- Modulation of conformational equilibrium by phosphorylation underlies the activation of deubiquitinase A.The Journal of biological chemistry · 2020Article
- Structure and regulation of human epithelial cell transforming 2 protein.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Structural Insights into the Regulation Mechanism of Small GTPases by GEFs.Molecules (Basel, Switzerland) · 2019Review
- Genetic alterations affecting GTPases and T-cell receptor signaling in peripheral T-cell lymphomas.Small GTPases · 2019Review
- Atomic view of the energy landscape in the allosteric regulation of Abl kinase.Nature structural & molecular biology · 2017Article
- The Tiam1 guanine nucleotide exchange factor is auto-inhibited by its pleckstrin homology coiled-coil extension domain.The Journal of biological chemistry · 2017Article
- NMR Methods to Study Dynamic Allostery.PLoS computational biology · 2016Review
- Analysis of Multidomain Protein Dynamics.Journal of chemical theory and computation · 2016Article
- Targeting the cyclophilin domain of Ran-binding protein 2 (Ranbp2) with novel small molecules to control the proteostasis of STAT3, hnRNPA2B1 and M-opsin.ACS chemical neuroscience · 2015Article
- Structural basis for catalytically restrictive dynamics of a high-energy enzyme state.Nature communications · 2015Article
- Intrinsically disordered proteins in cellular signalling and regulation.Nature reviews. Molecular cell biology · 2015Review
- Lipid and Protein Co-Regulation of PI3K Effectors Akt and Itk in Lymphocytes.Frontiers in immunology · 2015Review
1 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
Protein motions are important to activity, but quantitative relationships between internal dynamics and function are not well understood. The Dbl homology (DH) domain of the proto-oncoprotein and guanine nucleotide exchange factor Vav1 is autoinhibited through interactions between its catalytic surface and a helix from an N-terminal acidic region. Phosphorylation of the helix relieves autoinhibition. Here we show by NMR spectroscopy that the autoinhibited DH domain exists in equilibrium between a ground state, where the active site is blocked by the inhibitory helix, and an excited state, where the helix is dissociated. Across a series of mutants that differentially sample these states, catalytic activity of the autoinhibited protein and its rate of phosphorylation are linearly dependent on the population of the excited state. Thus, internal dynamics are required for and control both basal activity and the rate of full activation of the autoinhibited DH domain.
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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.