ArticleScientific reports2017
Computational and biochemical characterization of two partially overlapping interfaces and multiple weak-affinity K-Ras dimers.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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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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Who cites it
64 citing papers in PubMed, 101 citations in OpenAlex.
- KRAS4a and KRAS4b show distinct lipid-dependent regulation of RAS-RAF membrane dynamics.The Journal of biological chemistry · 2026Article
- RAS-membrane interaction and oligomerization: there is more than meets the eye.Biochemical Society transactions · 2025Review
- Membrane-Driven Dimerization of the Peripheral Membrane Protein KRAS: Implications for Downstream Signaling.International journal of molecular sciences · 2024Review
- Structural insights into the complex of oncogenic KRas4BLife science alliance · 2024Article
- Structural and functional analyses of a germline KRAS T50I mutation provide insights into Raf activation.JCI insight · 2023Article
- CD40 induces selective routing of Ras isoforms to subcellular compartments.Journal of cell communication and signaling · 2023Article
- Article
- Direct Observation of Membrane-Associated H-Ras in the Native Cellular Environment by In-CellJACS Au · 2023Article
- Machine Learning-Driven Multiscale Modeling: Bridging the Scales with a Next-Generation Simulation Infrastructure.Journal of chemical theory and computation · 2023Article
- Consensus on the RAS dimerization hypothesis: Strong evidence for lipid-mediated clustering but not for G-domain-mediated interactions.Molecular cell · 2023Review
- α4-α5 Helices on Surface of KRAS Can Accommodate Small Compounds That Increase KRAS Signaling While Inducing CRC Cell Death.International journal of molecular sciences · 2023Article
- Exploring CRD mobility during RAS/RAF engagement at the membrane.Biophysical journal · 2022Article
- Millisecond molecular dynamics simulations of KRas-dimer formation and interfaces.Biophysical journal · 2022Article
- Computer-Aided Drug Design Boosts RAS Inhibitor Discovery.Molecules (Basel, Switzerland) · 2022Review
- Review
- Machine learning-driven multiscale modeling reveals lipid-dependent dynamics of RAS signaling proteins.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- First Principles Calculation of Protein-Protein Dimer Affinities of ALS-Associated SOD1 Mutants.Frontiers in molecular biosciences · 2022Article
- Oncogenic KRAS G12D mutation promotes dimerization through a second, phosphatidylserine-dependent interface: a model for KRAS oligomerization.Chemical science · 2021Article
- A structural model of a Ras-Raf signalosome.Nature structural & molecular biology · 2021Article
- Review
4 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Recent studies found that membrane-bound K-Ras dimers are important for biological function. However, the structure and thermodynamic stability of these complexes remained unknown because they are hard to probe by conventional approaches. Combining data from a wide range of computational and experimental approaches, here we describe the structure, dynamics, energetics and mechanism of assembly of multiple K-Ras dimers. Utilizing a range of techniques for the detection of reactive surfaces, protein-protein docking and molecular simulations, we found that two largely polar and partially overlapping surfaces underlie the formation of multiple K-Ras dimers. For validation we used mutagenesis, electron microscopy and biochemical assays under non-denaturing conditions. We show that partial disruption of a predicted interface through charge reversal mutation of apposed residues reduces oligomerization while introduction of cysteines at these positions enhanced dimerization likely through the formation of an intermolecular disulfide bond. Free energy calculations indicated that K-Ras dimerization involves direct but weak protein-protein interactions in solution, consistent with the notion that dimerization is facilitated by membrane binding. Taken together, our atomically detailed analyses provide unique mechanistic insights into K-Ras dimer formation and membrane organization as well as the conformational fluctuations and equilibrium thermodynamics underlying these processes.
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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.