The DOI matches its Crossref record; 68 of the 68 references it cites were found in a registry or an index.
Ras activation by SOS: Allosteric regulation by altered fluctuation dynamics
Open accessAbstract
Outliers dominate signaling at cell membrane: SOS enzymes act at cell membranes to activate Ras, a regulatory protein often overactive in cancer cells. Iversen et al. devised a system where they could observe the activity of individual enzymes at work. The single SOS molecules occupied stable states that varied greatly in their catalytic activity. Regulation appeared to occur by altering the time spent in active states. The overall activity of SOS was determined by just a few molecules that achieved the highest catalytic activity. The methods described should allow further detailed kinetic analysis of this and other signaling events that occur at the cell membrane — properties that it is not possible to discern from bulk biochemical measurements. Science , this issue p. 50
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“GTP’s guanine riboside and ribose fractions then begin to bind to RAS, followed by the interaction of the γ-phosphate group of GTP with the magnesium cofactor of RAS, resulting in another conformational change of RAS and the detachment of SOS from the complex.333”
From Recent advances in targeting the “undruggable” proteins: from drug discovery to clinical trials (2023) · cites this paper as [333]
In the citing paper
“It has been shown that SOS functional output may be determined by the dynamical spectrum of rates sampled by a small number of enzymes, rather than the ensemble average.472”
From Protein Ensembles: How Does Nature Harness Thermodynamic Fluctuations for Life? The Diverse Functional Roles of Conformational Ensembles in the Cell (2016) · cites this paper as [472]
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Cites
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KRAS Mutation: From Undruggable to Druggable in Cancer
Huang, L., Guo, Z., Wang, F., & Fu, L. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00780-4 · Cited by 1,127
Wei, G., Xi, W., Nussinov, R., & Ma, B. (2016) · Chemical Reviews · doi:10.1021/acs.chemrev.5b00562 · Cited by 436
Recent 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
Snead, W. T., & Gladfelter, A. S. (2019) · Molecular Cell · doi:10.1016/j.molcel.2019.09.016 · Cited by 356
Ras Conformational Ensembles, Allostery, and Signaling
Lu, S., Jang, H., Muratcioglu, S., Gursoy, A., Keskin, O., Nussinov, R., & Zhang, J. (2016) · Chemical Reviews · doi:10.1021/acs.chemrev.5b00542 · Cited by 355
Metadata
- Authors
- Iversen, L., Tu, H.-L., Lin, W.-C., Christensen, S. M., Abel, S. M., Iwig, J., Wu, H.-J., Gureasko, J., Rhodes, C., Petit, R. S., Hansen, S. D., Thill, P., Yu, C.-H., Stamou, D., Chakraborty, A. K., Kuriyan, J., & Groves, J. T.
- Affiliations
- Howard Hughes Medical Institute (US)
- Massachusetts Institute of Technology (US)
- University of California, Berkeley (US)
- National University of Singapore (SG)
- University of Copenhagen (DK)
- Ragon Institute of MGH, MIT and Harvard (US)
- Corresponding author
- Iversen, Lars
- Tu, Hsiung-Lin
- Groves, Jay T.
- ORCID
- Venue
- Science
- Published
- 2014-07-04
- Volume
- 345
- Issue
- 6192
- Pages
- 50-54
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC4255705
- OpenAlex
- W2043601243
- Cited by
- 154
- References
- 68
- Citations by year
- 2026: 12 · 2025: 12 · 2024: 11 · 2023: 12 · 2022: 11 · 2021: 15 · 2020: 4 · 2019: 15 · 2018: 15 · 2017: 5 · 2016: 27 · 2015: 10 · 2014: 5
- FWCI
- 6.39
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- The HKU Scholars Hub (University of Hong Kong) (submittedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- National University of Singapore
- Danmarks Frie Forskningsfond
- Mechanobiology Institute, Singapore
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases (P01AI091580)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Advanced Fluorescence Microscopy Techniques
- Keywords
- H-Ras, Son of Sevenless, SO, small GTPase activation, allosteric regulation, nucleotide exchange, single-molecule kinetics, stochastic fluctuations, Ras-GTP, signal transduction, enzyme turnover rate
- MeSH terms
- Allosteric Regulation, Enzyme Activation, Humans, Kinetics, Nucleotides, Proto-Oncogene Proteins p21(ras), Crystallography, X-Ray, Catalytic Domain, Son of Sevenless Protein, Drosophila, Protein Interaction Domains and Motifs
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