Article
- The EMBO Journal (2005) 24, 3985 - 3995
- doi:10.1038/sj.emboj.7600858
Published online: 27 October 2005
Subject Categories:
Structure of the split PH domain and distinct lipid-binding properties of the PH–PDZ supramodule of 
-syntrophin
Jing Yan1,a, Wenyu Wen1,a, Weiguang Xu1, Jia-fu Long1, Marvin E Adams2, Stanley C Froehner2 and Mingjie Zhang1
- Department of Biochemistry, Molecular Neuroscience Center, Hong Kong University of Science and Technology, Hong Kong, People's Republic of China
- Department of Physiology and Biophysics, University of Washington, Seattle, Washington, DC, USA
Correspondence to:
Mingjie Zhang, Department of Biochemistry, Molecular Neuroscience Center, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, People's Republic of China. Tel.: +852 2358 8709; Fax: +852 2358 1552; E-mail: mzhang@ust.hk
aThese two authors contributed equally to this work
Received 6 April 2005; Accepted 10 October 2005
Abstract
Pleckstrin homology (PH) domains play diverse roles in cytoskeletal dynamics and signal transduction. Split PH domains represent a unique subclass of PH domains that have been implicated in interactions with complementary partial PH domains 'hidden' in many proteins. Whether partial PH domains exist as independent structural units alone and whether two halves of a split PH domain can fold together to form an intact PH domain are not known. Here, we solved the structure of the PHN–PDZ–PHC tandem of 
-syntrophin. The split PH domain of -syntrophin adopts a canonical PH domain fold. The isolated partial PH domains of -syntrophin, although completely unfolded, remain soluble in solution. Mixing of the two isolated domains induces de novo folding and yields a stable PH domain. Our results demonstrate that two complementary partial PH domains are capable of binding to each other to form an intact PH domain. We further showed that the PHN–PDZ–PHC tandem forms a functionally distinct supramodule, in which the split PH domain and the PDZ domain function synergistically in binding to inositol phospholipids.
Keywords:
- lipid binding,
- PDZ domain,
- split PH domain,
- supramodule,
- syntrophin
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