The modular logic of signaling proteins: building allosteric switches from simple binding domains
Abstract
Many eukaryotic signal transduction proteins have component-based architectures: they are built from combinations of protein interaction domains and catalytic domains. Intact, these proteins display the sophisticated allosteric behavior required for cellular regulation; the protein's output activity is tightly repressed under basal conditions, but can be robustly activated by a specific set of input effector ligands. A combination of structural, biophysical and computational studies is beginning to shed light on the fundamental principles governing this type of modular allostery.
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Signal integration through inter-domain linkers often shows synergistic rather than simple additive responses to activating inputs.
“Biological signal integration through the inter-domain linkage often does not display simple additive responses to activating inputs; instead, the linker provides synergistic activation effects.217”
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 [217]
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- Authors
- Lim, W. A.
- Affiliations
- University of California, San Francisco (US)
- Corresponding author
- Lim, Wendell A
- ORCID
- Lim, Wendell A
- Venue
- Current Opinion in Structural Biology
- Publisher
- Elsevier BV
- Published
- 2002-02
- Volume
- 12
- Issue
- 1
- Pages
- 61-68
- ISSN
- 0959-440X (ISSN-L)
- OpenAlex
- W2021209514
- Cited by
- 151
- References
- 52
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 6 · 2023: 4 · 2022: 3 · 2021: 5 · 2020: 1 · 2019: 3 · 2018: 3 · 2017: 2 · 2016: 2 · 2015: 2 · 2014: 6 · 2013: 4 · 2012: 9
- FWCI
- 0.89
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Current Opinion in Structural Biology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- 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
- Keywords
- allosteric regulation, signal transduction proteins, protein-protein interaction domains, catalytic domain, binding domain, protein structure-function relationship
- MeSH terms
- Allosteric Regulation, Allosteric Site, Animals, Binding Sites, Humans, Ligands, Protein Conformation, Proteins, Thermodynamics, Signal Transduction, Protein Structure, Tertiary, src-Family Kinases, Wiskott-Aldrich Syndrome Protein
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