Structure and phosphatidylinositol-(3,4)-bisphosphate binding of the C-terminal 
PH domain of human pleckstrin

Edlich, C.; Stier, Gunter; Simon, Bernd; Sattler, Michael; Muhle-Goll, Claudia

doi:10.1016/j.str.2004.11.012

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Structure and phosphatidylinositol-(3,4)-bisphosphate binding of the C-terminal PH domain of human pleckstrin

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Stier, Gunter
Department of Biomolecular Mechanisms, Max Planck Institute for Medical Research, Max Planck Society;

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Muhle-Goll, Claudia
Department of Biomolecular Mechanisms, Max Planck Institute for Medical Research, Max Planck Society;

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https://www.sciencedirect.com/science/article/pii/S0969212605000237/pdfft?md5=f0cff6d812e8aeb6e0343c04db6c0f8e&pid=1-s2.0-S0969212605000237-main.pdf
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Citation

Edlich, C., Stier, G., Simon, B., Sattler, M., & Muhle-Goll, C. (2005). Structure and phosphatidylinositol-(3,4)-bisphosphate binding of the C-terminal PH domain of human pleckstrin. Structure, 13(2), 277-286. doi:10.1016/j.str.2004.11.012.

Cite as: https://hdl.handle.net/21.11116/0000-0002-4FCC-1

Abstract

Pleckstrin is the major target of protein kinase C (PKC) in blood platelets. Its phosphorylation triggers responses that ultimately lead to platelet activation and blood clot formation. Pleckstrin consists of three domains: a pleckstrin homology (PH) domain at both termini and a central DEP (Dishevelled, Egl-1, Pleckstrin) domain. Here, we report the solution nuclear magnetic resonance (NMR) structure of the C-terminal PH domain (C-PH) of human pleckstrin-1. We show that this PH domain binds phosphatidylinositol-3,4-bisphosphate (PtdIns(3,4)P2) with high specificity in protein lipid overlay assays. Using NMR titration experiments and mutational analysis, residues involved in binding to PtdIns(3,4)P2 are identified. The binding site is formed by a patch of basic residues from the beta1 and beta2 strands and the beta1-beta2 loop. Since PtdIns(3,4)P2 is an important signaling molecule in platelets, our data suggest a C-PH dependent regulation of pleckstrin function in response to PtdIns(3,4)P2.