The DOI matches its Crossref record; 119 of the 119 references it cites were found in a registry or an index.
Dynamic Allostery: Linkers Are Not Merely Flexible
Open accessAbstract
Most proteins consist of multiple domains. How do linkers efficiently transfer information between sites that are on different domains to activate the protein? Mere flexibility only implies that the conformations would be sampled. For fast timescales between triggering events and cellular response, which often involves large conformational change, flexibility on its own may not constitute a good solution. We posit that successive conformational states along major allosteric propagation pathways are pre-encoded in linker sequences where each state is encoded by the previous one. The barriers between these states that are hierarchically populated are lower, achieving faster timescales even for large conformational changes. We further propose that evolution has optimized the linker sequences and lengths for efficiency, which explains why mutations in linkers may affect protein function and review the literature in this light.
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“The sequence of the linkers and of residues in contact between linkers and adjoining domains may encode successive or parallel states through which signals travel.29”
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 [29]
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Self-citationDetecting Protein Function and Protein-Protein Interactions from Genome Sequences
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Is allostery an intrinsic property of all dynamic proteins?
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Self-citationCsermely, P., Palotai, R., & Nussinov, R. (2010) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2010.04.009 · Cited by 821
Self-citationDuda, D. M., Borg, L. A., Scott, D. C., Hunt, H. W., Hammel, M., & Schulman, B. A. (2008) · Cell · doi:10.1016/j.cell.2008.07.022 · Cited by 767
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Self-citationThe Role of Protein Loops and Linkers in Conformational Dynamics and Allostery
Papaleo, E., Saladino, G., Lambrughi, M., Lindorff‐Larsen, K., Gervasio, F. L., & Nussinov, R. (2016) · Chemical Reviews · doi:10.1021/acs.chemrev.5b00623 · Cited by 434
Self-citationEmerging Computational Methods for the Rational Discovery of Allosteric Drugs
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Metadata
- Authors
- Ma, B., Tsai, C.-J., Haliloğlu, T., & Nussinov, R.
- Affiliations
- National Cancer Institute (US)
- Tel Aviv University (IL)
- Corresponding author
- Nussinov, Ruth
- Venue
- Structure
- Publisher
- Elsevier BV
- Published
- 2011-07
- Volume
- 19
- Issue
- 7
- Pages
- 907-917
- ISSN
- 0969-2126 (ISSN-L)
- PMC
- PMC6361528
- OpenAlex
- W2112600835
- Cited by
- 222
- References
- 119
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 6 · 2023: 8 · 2022: 10 · 2021: 15 · 2020: 10 · 2019: 15 · 2018: 10 · 2017: 12 · 2016: 17 · 2015: 29 · 2014: 24 · 2013: 23 · 2012: 19
- FWCI
- 2.18
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Structure (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Health and Human Services
- Türkiye Bilimler Akademisi
- National Institutes of Health (HHSN261200800001C)
- National Cancer Institute (HHSN261200800001E))
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- dynamic allostery, protein linkers, protein domains, conformational change, protein activation
- MeSH terms
- Allosteric Regulation, Allosteric Site, Animals, Binding Sites, Humans, Models, Molecular, Plants, Protein Binding, Proteins, Thermodynamics, Signal Transduction, Protein Structure, Tertiary, Protein Subunits
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