The phosphoinositide binding Phox Homology domain of yeast sorting nexin Vps17p
The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. Vsp17p forms a dimer with Vps5p, the yeast counterpart of human SNX1, and is part of the retromer complex that mediates the transport of the carboxypeptidase Y receptor Vps10p from endosomes to Golgi. Similar to Vps5p and SNX1, Vps17p harbors a Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature, C-terminal to the PX domain. The PX-BAR structural unit helps determine specific membrane localization.
Feature 1:putative phosphoinositide binding site [chemical binding site]
Evidence:
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.
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