The DOI matches its Crossref record; 458 of the 458 references it cites were found in a registry or an index.
Ras Conformational Ensembles, Allostery, and Signaling
Abstract
Ras proteins are classical members of small GTPases that function as molecular switches by alternating between inactive GDP-bound and active GTP-bound states. Ras activation is regulated by guanine nucleotide exchange factors that catalyze the exchange of GDP by GTP, and inactivation is terminated by GTPase-activating proteins that accelerate the intrinsic GTP hydrolysis rate by orders of magnitude. In this review, we focus on data that have accumulated over the past few years pertaining to the conformational ensembles and the allosteric regulation of Ras proteins and their interpretation from our conformational landscape standpoint. The Ras ensemble embodies all states, including the ligand-bound conformations, the activated (or inactivated) allosteric modulated states, post-translationally modified states, mutational states, transition states, and nonfunctional states serving as a reservoir for emerging functions. The ensemble is shifted by distinct mutational events, cofactors, post-translational modifications, and different membrane compositions. A better understanding of Ras biology can contribute to therapeutic strategies.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Designing PPI inhibitors to block the interaction of RAS and RAS effect factors represents a promising paradigm for modulating RAS function and provides new impetus for the discovery of related drugs.86,326–329”
From Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials (2023) · cites this paper as [327]
Citations
Cites
The phosphoinositide 3-kinase pathway
Cantley, L. C. (2002) · Science · doi:10.1126/science.296.5573.1655 · Cited by 5,621
Barbacid, M. (1987) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.56.070187.004023 · Cited by 3,885
The GTPase superfamily: conserved structure and molecular mechanism
Bourne, H. R., Sanders, D. A., & McCormick, F. (1991) · Nature · doi:10.1038/349117a0 · Cited by 3,392
Targeting RAS signalling pathways in cancer therapy
Downward, J. (2003) · Nature reviews. Cancer · doi:10.1038/nrc969 · Cited by 3,354
The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism
Engelman, J. A., Luo, J., & Cantley, L. C. (2006) · Nature Reviews Genetics · doi:10.1038/nrg1879 · Cited by 3,330
The Energy Landscapes and Motions of Proteins
Frauenfelder, H., Sligar, S. G., & Wolynes, P. G. (1991) · Science · doi:10.1126/science.1749933 · Cited by 3,250
Targeting the phosphoinositide 3-kinase pathway in cancer
Liu, P., Cheng, H.-L. M., Roberts, T. M., & Zhao, J. J. (2009) · Nature Reviews Drug Discovery · doi:10.1038/nrd2926 · Cited by 2,785
K-Ras(G12C) inhibitors allosterically control GTP affinity and effector interactions
Ostrem, J. M., Peters, U., Sos, M. L., Wells, J. A., & Shokat, K. M. (2013) · Nature · doi:10.1038/nature12796 · Cited by 2,557
Takai, Y., Sasaki, T., & Matozaki, T. (2001) · Physiological Reviews · doi:10.1152/physrev.2001.81.1.153 · Cited by 2,511
COSMIC: mining complete cancer genomes in the Catalogue of Somatic Mutations in Cancer
Forbes, S. A., Bindal, N., Bamford, S., Cole, C., Kok, C. Y., Beare, D., Jia, M., Shepherd, R., Leung, K., Menzies, A., et al. (2011) · Nucleic Acids Research · doi:10.1093/nar/gkq929 · Cited by 2,278
Research works printed but not linked: 1
- Bernard V., 2014, Int. J. Clin. Exp. Pathol., 7, 1667
Cited by
Sorted by citations
Tumor biomarkers for diagnosis, prognosis and targeted therapy
Zhou, Y., Tao, L., Qiu, J., Xu, J., Yang, X., Zhang, Y., Tian, X., Guan, X., Cen, X., & Zhao, Y. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01823-2 · Cited by 836
Anticancer drug resistance: An update and perspective
Nussinov, R., Tsai, C., & Jang, H. (2021) · Drug Resistance Updates · doi:10.1016/j.drup.2021.100796 · Cited by 410
Self-citationRecent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials
Xie, X., Yu, T., Li, X., Zhang, N., Foster, L. J., Peng, C., Huang, W., & He, G. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01589-z · Cited by 396
A model for RAS mutation patterns in cancers: finding the sweet spot
Li, S., Balmain, A., & Counter, C. M. (2018) · Nature Reviews Cancer · doi:10.1038/s41568-018-0076-6 · Cited by 384
Targeted protein degradation: advances in drug discovery and clinical practice
Zhong, G., Chang, X., Xie, W., & Zhou, X. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-02004-x · Cited by 326
Metadata
- Authors
- Lu, S., Jang, H., Muratcioglu, S., Gursoy, A., Keskin, O., Nussinov, R., & Zhang, J.
- Affiliations
- Shanghai Jiao Tong University (CN)
- Frederick National Laboratory for Cancer Research (US)
- Tel Aviv University (IL)
- Corresponding author
- Nussinov, Ruth
- Zhang, Jian
- Venue
- Chemical Reviews
- Publisher
- American Chemical Society (ACS)
- Published
- 2016-01-27
- Volume
- 116
- Issue
- 11
- Pages
- 6607-6665
- ISSN
- 0009-2665 (ISSN-L)
- 1520-6890
- OpenAlex
- W2260312731
- Cited by
- 355
- References
- 457
- Citations by year
- 2026: 23 · 2025: 26 · 2024: 30 · 2023: 40 · 2022: 47 · 2021: 35 · 2020: 39 · 2019: 38 · 2018: 29 · 2017: 30 · 2016: 18
- FWCI
- 3.46
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Chemical Reviews (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Program for New Century Excellent Talents in University (NCET-12-0355)
- National Cancer Institute (HHSN261200800001E)
- Ministry of Science and Technology of the People's Republic of China (2015CB910403)
- Science and Technology Commission of Shanghai Municipality (13QA1402300)
- National Natural Science Foundation of China (81302698, 81322046, 81473137)
- Shanghai Municipal Health and Family Planning Commission (20154Y0058)
- Collaborative Innovation Center of Systems Biomedicine
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Keywords
- Ras proteins, small GTPases, conformational ensembles, allosteric regulation, Ras signaling, guanine nucleotide exchange factor, GTPase-activating protein, post-translational modification, membrane composition, RAS mutations
- MeSH terms
- Allosteric Regulation, Guanosine Triphosphate, Protein Binding, Signal Transduction, Protein Structure, Tertiary, ras Proteins, Nuclear Magnetic Resonance, Biomolecular, Catalytic Domain
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
