To Cluster or Not to Cluster

Science's STKE  24 Jul 2007:
Vol. 2007, Issue 396, pp. tw265
DOI: 10.1126/stke.3962007tw265

The PDZ domain is a frequently occurring interaction domain in eukaryotic proteins that binds to the C termini of target proteins. PDZ domains have been thought to cluster into functional classes, each with distinct sequence binding preferences. Using a combination of experimental data and modeling, Stiffler et al. predict PDZ domain-peptide interactions across the mouse proteome. Instead of observing clustering, they find that PDZ domains are evenly distributed throughout selectivity space likely to minimize cross-reactivity. The study highlights focusing on families of interaction domains as a productive approach to gain insight into protein function.

M. A. Stiffler, J. R. Chen, V. P. Grantcharova, Y. Lei, D. Fuchs, J. E. Allen, L. A. Zaslavskaia, G. MacBeath, PDZ domain binding selectivity is optimized across the mouse proteome. Science 317, 364-369 (2007). [Abstract] [Full Text]