The phosphoinositide binding Phox Homology domain of Phospholipase D2
The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. Phospholipase D (PLD) catalyzes the hydrolysis of the phosphodiester bond of phosphatidylcholine to generate membrane-bound phosphatidic acid and choline. PLD activity has been detected in viruses, bacteria, yeast, plants, and mammals, but the PX domain is not present in PLDs from viruses and bacteria. PLDs are implicated in many cellular functions like signaling, cytoskeletal reorganization, vesicular transport, stress responses, and the control of differentiation, proliferation, and survival. PLD2 contains PX and Pleckstrin Homology (PH) domains in addition to the catalytic domain. It mediates EGF-dependent insulin secretion and EGF-induced Ras activation by the guanine nucleotide-exchange factor Son of sevenless (Sos). It regulates mast cell activation by associating and promoting the activation of the protein tyrosine kinase Syk. PLD2 also participates in the sphingosine 1-phosphate-mediated pathway that stimulates the migration of endothelial cells, an important factor in angiogenesis. The PX domain is involved in targeting of proteins to PI-enriched membranes, and may also be involved in protein-protein interaction.
Feature 1:phosphoinositide binding site [chemical binding site]
Comment:A majority of PX domain containing proteins binds phosphatidylinositol-3-phosphate (PI3P) at this site. In some cases, other phosphoinositides, such as PI4P or PI(3,4)P2, are the preferred substrates.
Comment:based on the structures of phosphatidylinositol-3-phosphate bound to other members of this superfamily
Comment:Two basic residues are key in binding with phosphoinositides: one forms hydrogen bonds with the 3-phosphate of PI(3)P and another forms hydrogen bonds with the 4-and 5-hydroxyl groups of PI(3)P.