ArticleScience (New York, N.Y.)2019
Cryo-EM structure of a dimeric B-Raf:14-3-3 complex reveals asymmetry in the active sites of B-Raf kinases.
Article in Science (New York, N.Y.), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 112 papers.
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Who cites it
112 citing papers in PubMed, 192 citations in OpenAlex.
- Benchmarking Boltz-2 for relative kinase-inhibitor interaction patterns across conformational states and resistance mutations.npj drug discovery · 2026Article
- Identification of Ywhab as a Candidate Downstream Target of Figla During Ovarian Reserve Establishment.Reproductive sciences (Thousand Oaks, Calif.) · 2026Article
- High-resolution measurement of ERK activation state reveals determinants of BRAF regulation and drug sensitivity.bioRxiv : the preprint server for biology · 2026Article
- A complex of MAST1 and 14-3-3η regulates Tau phosphorylation in the developing cortex.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Cryo-EM structure and biochemical characterization of a BRAF/CRAF heterodimer: Negative charge in the NtA motif is not required for RAF activation.bioRxiv : the preprint server for biology · 2026Article
- MEK interactions tune RAF kinase sensitivity to conformation-selective inhibition.Nature chemical biology · 2026Article
- Restoring the 14-3-3/CRAF regulatory interaction in Noonan syndrome using molecular glues.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Structural basis of the cyclin Y/14-3-3 protein-mediated activation of CDK16.Nature communications · 2026Article
- Modulation of the 14-3-3σ/C-RAF "Auto"inhibited Complex by Molecular Glues.Journal of the American Chemical Society · 2026Article
- Structural basis for pseudokinase-mediated regulation of GCN2 in the integrated stress response.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Molecular basis of mitogen-activated protein kinase ERK2 activation by its upstream kinase MEK1.bioRxiv : the preprint server for biology · 2026Article
- The BRAF-specific region suppresses cysteine-rich domain-lipid interaction independently of canonical autoinhibition by the 14-3-3 dimer.Protein science : a publication of the Protein Society · 2026Article
- BRAF mutation and tumor immune microenvironment in new era.American journal of cancer research · 2026Review
- DA-Raf synergistically binds to the plasma membrane and Ras to suppress ERK signaling.Life science alliance · 2025Article
- An in vitro BRAF activation assay elucidates molecular mechanisms driving disassembly of the autoinhibited BRAF state.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Stabilization of Native Protein-Protein Interactions with Molecular Glues: A 14-3-3 Case Study.Accounts of chemical research · 2025Article
- Cryo-EM structures of CRAF/MEK1/14-3-3 complexes in autoinhibited and open-monomer states reveal features of RAF regulation.Nature communications · 2025Article
- 14-3-3 binding maintains the Parkinson's associated kinase LRRK2 in an inactive state.Nature communications · 2025Article
- Mathematical modeling suggests 14-3-3 proteins modulate RAF paradoxical activation.PLoS computational biology · 2025Article
- A large-scale curated and filterable dataset for cryo-EM foundation model pre-training.Scientific data · 2025Article
52 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
Raf kinases are important cancer drug targets. Paradoxically, many B-Raf inhibitors induce the activation of Raf kinases. Cryo-electron microscopy structural analysis of a phosphorylated B-Raf kinase domain dimer in complex with dimeric 14-3-3, at a resolution of ~3.9 angstroms, shows an asymmetric arrangement in which one kinase is in a canonical "active" conformation. The distal segment of the C-terminal tail of this kinase interacts with, and blocks, the active site of the cognate kinase in this asymmetric arrangement. Deletion of the C-terminal segment reduces Raf activity. The unexpected asymmetric quaternary architecture illustrates how the paradoxical activation of Raf by kinase inhibitors reflects an innate mechanism, with 14-3-3 facilitating inhibition of one kinase while maintaining activity of the other. Conformational modulation of these contacts may provide new opportunities for Raf inhibitor development.
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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.