Allostery: Absence of a change in shape does not imply that allostery is not at play
Open accessAbstract
Allostery is essential for controlled catalysis, signal transmission, receptor trafficking, turning genes on and off, and apoptosis. It governs the organism's response to environmental and metabolic cues, dictating transient partner interactions in the cellular network. Textbooks taught us that allostery is a change of shape at one site on the protein surface brought about by ligand binding to another. For several years, it has been broadly accepted that the change of shape is not induced; rather, it is observed simply because a larger protein population presents it. Current data indicate that while side chains can reorient and rewire, allostery may not even involve a change of (backbone) shape. Assuming that the enthalpy change does not reverse the free-energy change due to the change in entropy, entropy is mainly responsible for binding.
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Crystal structures of KRAS G12X mutants display only minor differences.
“The crystal structures of KRAS G12X mutants display only minor differences”
The lack of structural differences does not exclude an allosteric effect of the mutation.
“but the lack of structural differences does not exclude the allosteric effect of the mutation [56].”
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- Authors
- Tsai, C.-J., del Sol, A., & Nussinov, R.
- Affiliations
- Tel Aviv University (IL)
- Corresponding author
- Nussinov, Ruth
- Venue
- Journal of Molecular Biology
- Publisher
- Elsevier BV
- Published
- 2008-04
- Volume
- 378
- Issue
- 1
- Pages
- 1-11
- ISSN
- 0022-2836 (ISSN-L)
- PMC
- PMC2684958
- OpenAlex
- W2095420958
- Cited by
- 453
- References
- 55
- Citations by year
- 2026: 14 · 2025: 14 · 2024: 5 · 2023: 15 · 2022: 11 · 2021: 13 · 2020: 13 · 2019: 20 · 2018: 19 · 2017: 21 · 2016: 35 · 2015: 24 · 2014: 42 · 2013: 47 · 2012: 38
- FWCI
- 3.16
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Molecular Biology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Open Repository and Bibliography (University of Luxembourg) (submittedVersion)
- Funders
- National Institutes of Health (n01co12400-79-0-22)
- National Cancer Institute (N01CO12400, Z01BC010440, N01-CO-012400)
- 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 › Biochemical and Molecular Research
- Keywords
- allosteric regulation, protein conformational change, ligand binding, entropy-driven binding, enthalpy-entropy compensation, protein shape, protein-ligand interactions
- MeSH terms
- Allosteric Regulation, Animals, Humans, Models, Molecular, Protein Conformation, Thermodynamics, Signal Transduction
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