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Updated: May 23, 2026

Annotation of Plant Gene Function via Combined Genomics, Metabolomics and Informatics
Published on: June 17, 2012
Genome-wide functional annotation of dual-specificity protein- and lipid-binding modules that regulate protein
Yong Chen1, Ren Sheng, Morten Källberg
1Department of Chemistry, University of Illinois at Chicago, Chicago, IL 60607, USA.
Abstract:
Emerging evidence indicates that membrane lipids regulate protein networking by directly interacting with protein-interaction domains (PIDs). As a pilot study to identify and functionally annodate lipid-binding PIDs on a genomic scale, we performed experimental and computational studies of PDZ domains. Characterization of 70 PDZ domains showed that ~40% had submicromolar membrane affinity. Using a computational model built from these data, we predicted the membrane-binding properties of 2,000 PDZ domains from 20 species. The accuracy of the prediction was experimentally validated for 26 PDZ domains. We also subdivided lipid-binding PDZ domains into three classes based on the interplay between membrane- and protein-binding sites. For different classes of PDZ domains, lipid binding regulates their protein interactions by different mechanisms. Functional studies of a PDZ domain protein, rhophilin 2, suggest that all classes of lipid-binding PDZ domains serve as genuine dual-specificity modules regulating protein interactions at the membrane under physiological conditions.
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