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1: Science. 2007 Jul 20;317(5836):364-9.
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Erratum in:
  • Science. 2007 Oct 19;318(5849):393.

PDZ domain binding selectivity is optimized across the mouse proteome.

Stiffler MA, Chen JR, Grantcharova VP, Lei Y, Fuchs D, Allen JE, Zaslavskaia LA, MacBeath G.

Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA 02138, USA.

PDZ domains have long been thought to cluster into discrete functional classes defined by their peptide-binding preferences. We used protein microarrays and quantitative fluorescence polarization to characterize the binding selectivity of 157 mouse PDZ domains with respect to 217 genome-encoded peptides. We then trained a multidomain selectivity model to predict PDZ domain-peptide interactions across the mouse proteome with an accuracy that exceeds many large-scale, experimental investigations of protein-protein interactions. Contrary to the current paradigm, PDZ domains do not fall into discrete classes; instead, they are evenly distributed throughout selectivity space, which suggests that they have been optimized across the proteome to minimize cross-reactivity. We predict that focusing on families of interaction domains, which facilitates the integration of experimentation and modeling, will play an increasingly important role in future investigations of protein function.

Publication Types:
PMID: 17641200 [PubMed - indexed for MEDLINE]