THE PLECKSTRIN HOMOLOGY DOMAIN OF PHOSPHOLIPASE C-DELTA 1 BINDS WITH HIGH AFFINITY TO PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE IN BILAYER MEMBRANES

摘要: The pleckstrin homology (PH) domain of phospholipase C-delta 1 (PLC-delta 1) binds to phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) in phospholipid membranes with an affinity (Ka approximately 10(6) M-1) and specificity comparable those the native enzyme. PLC-delta its PH also bind inositol 1,4,5-trisphosphate, polar head group PI(4,5)P2, 1:1 stoichiometry. A peptide corresponding amino acids 30-43 contains several basic residues predicted but weakly little for PI(4,5)P2; hence tertiary structure isolated is required high PI(4,5)P2 binding. Our PI-(4,5)P2 binding results support hypothesis that intact domain, serving as a specific tether, directs enriched permits active site, located elsewhere protein, hydrolyze multiple substrate molecules before this enzyme dissociates from membrane surface.