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The recognition of membrane‐bound PtdIns3 P by PX domains
Author(s) -
Jia ZhiGuang,
Ghai Rajesh,
Collins Brett M.,
Mark Alan E.
Publication year - 2014
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.24593
Subject(s) - membrane , chemistry , membrane protein , domain (mathematical analysis) , endocytic cycle , biophysics , crystallography , biochemistry , biology , receptor , mathematics , endocytosis , mathematical analysis
Phox‐homology (PX) domains target proteins to the organelles of the secretary and endocytic systems by binding to phosphatidylinositol phospholipids (PIPs). Among all the structures of PX domains that have been solved, only three have been solved in a complex with the main physiological ligand: PtdIns3 P . In this work, molecular dynamic simulations have been used to explore the structure and dynamics of the p40 phox –PX domain and the SNX17–PX domain and their interaction with membrane‐bound PtdIns3 P . In the simulations, both PX domains associated spontaneously with the membrane‐bound PtdIns3 P and formed stable complexes. The interaction between the p40 phox –PX domain and PtdIns3 P in the membrane was found to be similar to the crystal structure of the p40 phox –PX–PtdIns3 P complex that is available. The interaction between the SNX17–PX domain and PtdIns3 P was similar to that observed in the p40 phox –PX–PtdIns3 P complex; however, some residues adopted different orientations. The simulations also showed that nonspecific interactions between the β 1– β 2 loop and the membrane play an important role in the interaction of membrane bound PtdIns3 P and different PX domains. The behaviour of unbound PtdIns3 P within a 2‐oleoyl‐1‐palmitoyl‐ sn ‐glycero‐3‐phosphocholine (POPC) membrane environment was also examined and compared to the available experimental data and simulation studies of related molecules. Proteins 2014; 82:2332–2342. © 2014 Wiley Periodicals, Inc.