Pleckstrin homology domain 1 of mouse alpha 1-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 (PtdIns4,5P2). Half-maximal binding occurred at 1.9 microM PtdIns4,5P2 and when 1.2 PtdIns4,5P2 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 PtdIns4,5P2 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.
Chockalingam
P S
PS
Department of Biochemistry, University of Tennessee, Memphis 38163, USA.
Gee
S H
SH
Jarrett
H W
HW
D000595:Amino Acid Sequence; D000818:Animals; D001798:Blood Proteins / Q000378:metabolism*; D002135:Calcium-Binding Proteins; D002417:Cattle; D011232:Chemical Precipitation; D003956:Dialysis; D050356:Lipid Metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism*; D010750:Phosphoproteins; D011485:Protein Binding / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000138:chemical synthesis / Q000302:isolation & purification; D017386:Sequence Homology, Amino Acid; D014461:Ultracentrifugation
D001798:Blood Proteins; D002135:Calcium-Binding Proteins; D008565:Membrane Proteins; D009124:Muscle Proteins; D019269:Phosphatidylinositol 4,5-Diphosphate; D010750:Phosphoproteins; D011993:Recombinant Fusion Proteins; C039077:platelet protein P47; C091825:syntrophin alpha1