| Autor: |
Ren Sheng, Antonina Silkov, Yong Chen, Wonhwa Cho, Morten Källberg, Svetlana Kurilova, Barry Honig, Nitin Bhardwaj, Randy A. Hall, Moe P. Tun, Hui Lu |
| Rok vydání: |
2012 |
| Předmět: |
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| Zdroj: |
Molecular Cell. 46:226-237 |
| ISSN: |
1097-2765 |
| DOI: |
10.1016/j.molcel.2012.02.012 |
| Popis: |
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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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