ArticleChemical science2022
Equilibria between conformational states of the Ras oncogene protein revealed by high pressure crystallography.
Article in Chemical science, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 25 citations in OpenAlex.
- Functionally related internal fluctuations in human ileal bile acid-binding protein by high pressure nuclear magnetic resonance.Protein science : a publication of the Protein Society · 2026Article
- Macromolecular crystallography for mammalian body temperature in support of molecular biophysics methods.Biophysical reviews · 2025Review
- Differential Responses in the Core, Active Site and Peripheral Regions of Cytochrome c Peroxidase to Extreme Pressure and Temperature.Journal of molecular biology · 2024Article
- 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
- Conformational States of the GDP- and GTP-Bound HRAS Affected by A59E and K117R: An Exploration from Gaussian Accelerated Molecular Dynamics.Molecules (Basel, Switzerland) · 2024Article
- GTP-Bound N-Ras Conformational States and Substates Are Modulated by Membrane and Point Mutation.International journal of molecular sciences · 2024Article
- Pushed to extremes: distinct effects of high temperature versus pressure on the structure of STEP.Communications biology · 2024Article
- Article
- Reduced dynamic complexity allows structure elucidation of an excited state of KRASCommunications biology · 2023Article
- Pushed to extremes: distinct effects of high temperature vs. pressure on the structure of an atypical phosphatase.bioRxiv : the preprint server for biology · 2023Article
- FLEXR: automated multi-conformer model building using electron-density map sampling.Acta crystallographica. Section D, Structural biology · 2023Article
- Delineating the RAS Conformational Landscape.Cancer research · 2022Article
- Structural communication between the GTPase Sec4p and its activator Sec2p: Determinants of GEF activity and early deformations to nucleotide release.Computational and structural biotechnology journal · 2022Article
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In this work, we experimentally investigate the allosteric transitions between conformational states on the Ras oncogene protein using high pressure crystallography. Ras protein is a small GTPase involved in central regulatory processes occurring in multiple conformational states. Ras acts as a molecular switch between active GTP-bound, and inactive GDP-bound states, controlling essential signal transduction pathways. An allosteric network of interactions between the effector binding regions and the membrane interacting regions is involved in Ras cycling. The conformational states which coexist simultaneously in solution possess higher Gibbs free energy than the ground state. Equilibria between these states can be shifted by applying pressure favouring conformations with lower partial molar volume, and has been previously analyzed by high-pressure NMR spectroscopy. High-pressure macromolecular crystallography (HPMX) is a powerful tool perfectly complementary to high-pressure NMR, allowing characterization at the molecular level with a high resolution the different allosteric states involved in the Ras cycling. We observe a transition above 300 MPa in the crystal leading to more stable conformers. Thus, we compare the crystallographic structures of Ras(wt)·Mg
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