Evolving specificity from variability for protein interaction domains
Abstract
An important question in modular domain-peptide interactions, which play crucial roles in many biological processes, is how the diverse specificities exhibited by different members of a domain family are encoded in a common scaffold. Analysis of the Src homology (SH) 2 family has revealed that its specificity is determined, in large part, by the configuration of surface loops that regulate ligand access to binding pockets. In a distinct manner, SH3 domains employ loops for ligand recognition. The PDZ domain, in contrast, achieves specificity by co-evolution of binding-site residues. Thus, the conformational and sequence variability afforded by surface loops and binding sites provides a general mechanism by which to encode the wide spectrum of specificities observed for modular protein interaction domains.
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A coherent structural model of SH2 domain binding specificity has been suggested.
“This is in contrast to the systematically studied interactions between SH2 domains and linear motifs for which a coherent structural model of SH2 domain binding specificity has been suggested (17-18).”
From Specificity of Linear Motifs That Bind to a Common Mitogen-Activated Protein Kinase Docking Groove (2012) · cites this paper as [18]
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- Authors
- Kaneko, T., Sidhu, S. S., & Li, S. S. C.
- Affiliations
- Western University (CA)
- University of Toronto (CA)
- Corresponding author
- Li, Shawn S.C.
- Venue
- Trends in Biochemical Sciences
- Publisher
- Elsevier BV
- Published
- 2011-04
- Volume
- 36
- Issue
- 4
- Pages
- 183-190
- ISSN
- 0968-0004 (ISSN-L)
- OpenAlex
- W2081076958
- Cited by
- 45
- References
- 82
- Citations by year
- 2026: 1 · 2024: 3 · 2022: 2 · 2021: 1 · 2020: 1 · 2019: 3 · 2018: 6 · 2017: 2 · 2016: 1 · 2015: 2 · 2014: 4 · 2013: 3 · 2012: 14
- FWCI
- 0.67
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Trends in Biochemical Sciences (publishedVersion)
- PubMed (publishedVersion)
- Scholarship@Western (Western University) (submittedVersion)
- Funders
- Genome Canada
- Ontario Genomics Institute
- Canada Research Chairs
- Canadian Institutes of Health Research (93684_1)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chemical Synthesis and Analysis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- protein-protein interaction domains, domain specificity, modular protein domains, SH2 domain, SH3 domain, PDZ domain, surface loops, binding site evolution, coevolution, ligand recognition, sequence variation
- MeSH terms
- Humans, Ligands, Models, Molecular, Proteins, Substrate Specificity, Protein Interaction Domains and Motifs
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