Cited by 45Protein Structure and DynamicsChemical Synthesis and AnalysisProtein Kinase Regulation and GTPase Signaling

Evolving specificity from variability for protein interaction domains

Kaneko, Tomonori, Sidhu, Sachdev S., Li, Shawn S.C.·2011·Trends in Biochemical Sciences

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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Crossref · 10.1016/j.tibs.2010.12.001

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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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