1XX0

Structure of the C-terminal PH domain of human pleckstrin

Summary for 1XX0

• Entry DOI: 10.2210/pdb1xx0/pdb
• Descriptor: Pleckstrin (1 entity in total)
• Functional Keywords: pleckstrin, ph, c-terminal, pleckstrin homology, lipid binding protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 1
• Total formula weight: 14795.97

Authors

Edlich, C.,Stier, G.,Simon, B.,Sattler, M.,Muhle-Goll, C. (deposition date: 2004-11-03, release date: 2005-05-03, Last modification date: 2024-05-29)

Primary citation

Edlich, C.,Stier, G.,Simon, B.,Sattler, M.,Muhle-Goll, C.
Structure and phosphatidylinositol-(3,4)-bisphosphate binding of the C-terminal PH domain of human pleckstrin
STRUCTURE, 13:277-286, 2005

PubMed 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.

PubMed: 15698571
DOI: 10.1016/j.str.2004.11.012

Experimental method

SOLUTION NMR