Pleckstrin homology domain 1 of mouse α1-syntrophin binds phosphatidylinositol 4,5-bisphosphate

Mouse alpha 1-syntrophin sequences were produced as chimeric fusion proteins in bacteria and found to bind phosphatidylinositol 4,5-bisphosphate (PtdIns4,5P(2)). Half-maximal binding occurred at 1.9 mu M PtdIns4,5P(2) and when 1.2 PtdIns4,5P(2) were added per syntrophin. Binding was specific for PtdIns4,5P2 and did not occur with six other tested lipids including the similar phosphatidylinositol 4-phosphate. Binding was localized to the N-terminal pleckstrin homology domain (PH1); the second, C-terminal PH2 domain did not bind lipids. Key residues in PtdIns4,5P(2) binding to a PH domain were found to be conserved in alpha-syntrophins' PH1 domains and absent in PH2 domains, suggesting a molecular basis for binding.