ArticleBiomolecules2021
Crystal Structure Reveals the Full Ras-Raf Interface and Advances Mechanistic Understanding of Raf Activation.
Article in Biomolecules, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 69 citations in OpenAlex.
- Divergent CRD-Dependent Mechanisms Govern RAS Isoform-Selective Recruitment of CRAF and ARAF.bioRxiv : the preprint server for biology · 2026Article
- Revisiting RAS family GTPase signaling: effector selectivity and oncogenic bypass.The Biochemical journal · 2026Review
- De Novo Protein Design Enables Targeting of Intractable Oncogenic Protein-Protein Interfaces.Biologics (Basel, Switzerland) · 2026Article
- Positive cooperativity between RAS-binding and cysteine-rich domains regulates RAF membrane binding kinetics via lateral rebinding.Nature communications · 2026Article
- Identification and characterization of binders to a cryptic and functional pocket in KRAS.Nature communications · 2025Article
- De novo protein design enables targeting of intractable oncogenic interfaces.bioRxiv : the preprint server for biology · 2025Article
- Allostery in Disease: Anticancer Drugs, Pockets, and the Tumor Heterogeneity Challenge.Journal of molecular biology · 2025Review
- Sequence Determinants of Allosteric Back-to-front Control of the Arf Nucleotide Switch.Journal of molecular biology · 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
- Pioneer in Molecular Biology: Conformational Ensembles in Molecular Recognition, Allostery, and Cell Function.Journal of molecular biology · 2025Review
- Effector Binding Sequentially Alters KRAS Dimerization on the Membrane: New Insights Into RAS-Mediated RAF Activation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Functional and structural insights into RAS effector proteins.Molecular cell · 2024Review
- Regulation of RAF family kinases: new insights from recent structural and biochemical studies.Biochemical Society transactions · 2024Review
- RAS and SHOC2 Roles in RAF Activation and Therapeutic Considerations.Annual review of cancer biology · 2024Article
- Reconstitution and characterization of BRAF in complex with 14-3-3 and KRAS4B on nanodiscs.Protein science : a publication of the Protein Society · 2024Article
- Membrane-Driven Dimerization of the Peripheral Membrane Protein KRAS: Implications for Downstream Signaling.International journal of molecular sciences · 2024Review
- Comparative analysis of KRAS4a and KRAS4b splice variants reveals distinctive structural and functional properties.Science advances · 2024Article
- Unveiling the domain-specific and RAS isoform-specific details of BRAF kinase regulation.eLife · 2023Article
- Kinetic and thermodynamic allostery in the Ras protein family.Biophysical journal · 2023Article
- Structural insights into the role of SHOC2-MRAS-PP1C complex in RAF activation.The FEBS journal · 2023Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Ras and Raf-kinase interact through the Ras-binding (RBD) and cysteine-rich domains (CRD) of Raf to signal through the mitogen-activated protein kinase pathway, yet the molecular mechanism leading to Raf activation has remained elusive. We present the 2.8 Å crystal structure of the HRas-CRaf-RBD_CRD complex showing the Ras-Raf interface as a continuous surface on Ras, as seen in the KRas-CRaf-RBD_CRD structure. In molecular dynamics simulations of a Ras dimer model formed through the α4-α5 interface, the CRD is dynamic and located between the two Ras protomers, poised for direct or allosteric modulation of functionally relevant regions of Ras and Raf. We propose a molecular model in which Ras binding is involved in the release of Raf autoinhibition while the Ras-Raf complex dimerizes to promote a platform for signal amplification, with Raf-CRD centrally located to impact regulation and function.
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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.