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Sci. Signal., 8 September 2009
Vol. 2, Issue 87, p. ra50
[DOI: 10.1126/scisignal.2000416]

RESEARCH ARTICLES

Editor's Summary

Expanding the Universe of PDZ Domains
PDZ domains are peptide recognition modules that typically recognize specific C-terminal sequences, and scaffold proteins containing these domains are important for organizing specialized cellular structures, such as epithelial junctions, neuronal postsynaptic densities, and immunological synapses. PDZ domains exhibit limited sequence conservation; thus Ernst et al. developed a set of PDZ domain variants to study how this family can evolve to produce domains with different binding specificities. They show that random mutations in the binding site of the Erbin PDZ domain produce stable PDZ domains that have specificities that are either similar to those in nature or are new specificities not found in naturally occurring PDZ domains. A selective pressure for ligand binding was not required to produce PDZ variants that bound ligands. The presence of specificities not found in nature suggests that nature has not exhausted the specificity potential of the PDZ fold and that these domains may continue to evolve, leading to new networks of protein interactions. Alternatively, protein interaction networks may be experimentally rewired by synthetic PDZ domains.

Citation: A. Ernst, S. L. Sazinsky, S. Hui, B. Currell, M. Dharsee, S. Seshagiri, G. D. Bader, S. S. Sidhu, Rapid Evolution of Functional Complexity in a Domain Family. Sci. Signal. 2, ra50 (2009).

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THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Stereochemical Determinants of C-terminal Specificity in PDZ Peptide-binding Domains: A NOVEL CONTRIBUTION OF THE CARBOXYLATE-BINDING LOOP.
J. F. Amacher, P. R. Cushing, C. D. Bahl, T. Beck, and D. R. Madden (2013)
J. Biol. Chem. 288, 5114-5126
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A regression framework incorporating quantitative and negative interaction data improves quantitative prediction of PDZ domain-peptide interaction from primary sequence.
X. Shao, C. S. H. Tan, C. Voss, S. S. C. Li, N. Deng, and G. D. Bader (2011)
Bioinformatics 27, 383-390
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Signals: Tinkering with Domains.
E. Bornberg-Bauer (2010)
Science Signaling 3, pe31
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