The recognition of membrane-bound PtdIns3P by PX domains.
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: PtdIns3P. 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 PtdIns3P. In the simulations, both PX domains associated spontaneously with the membrane-bound PtdIns3P and formed stable complexes. The interaction between the p40(phox) -PX domain and PtdIns3P in the membrane was found to be similar to the crystal structure of the p40(phox) -PX-PtdIns3P complex that is available. The interaction between the SNX17-PX domain and PtdIns3P was similar to that observed in the p40(phox) -PX-PtdIns3P complex; however, some residues adopted different orientations. The simulations also showed that nonspecific interactions between the β1-β2 loop and the membrane play an important role in the interaction of membrane bound PtdIns3P and different PX domains. The behaviour of unbound PtdIns3P 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.
School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queens Land, 4072, Australia.
ZhiGuang
Z
Jia
Rajesh
R
Ghai
Brett M
BM
Collins
Alan E
AE
Mark
D002462:Cell Membrane / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D019255:NADPH Oxidases / Q000737:chemistry / Q000378:metabolism*; D018129:Phosphatidylinositol Phosphates / Q000737:chemistry / Q000378:metabolism*; D011487:Protein Conformation; D058305:Sorting Nexins / Q000737:chemistry / Q000378:metabolism*
D008024:Ligands; D018129:Phosphatidylinositol Phosphates; C487895:SNX17 protein, human; D058305:Sorting Nexins; C055525:phosphatidylinositol 3-phosphate; D019255:NADPH Oxidases; C113333:NCF4 protein, human
GROMACS; GROMOS; Phox-homology proteins; SNX17; membrane-binding protein; molecular simulation; p40phox; phosphatidylinositol phospholipids