title: The structure of myristoylated Mason-Pfizer monkey virus matrix protein and the role of phosphatidylinositol-(4,5)-bisphosphate in its membrane binding.
abstract: We determined the solution structure of myristoylated Mason-Pfizer monkey virus matrix protein by NMR spectroscopy. The myristoyl group is buried inside the protein and causes a slight reorientation of the helices. This reorientation leads to the creation of a binding site for phosphatidylinositols. The interaction between the matrix protein and phosphatidylinositols carrying C(8) fatty acid chains was monitored by observation of concentration-dependent chemical shift changes of the affected amino acid residues, a saturation transfer difference experiment and changes in (31)P chemical shifts. No differences in the binding mode or affinity were observed with differently phosphorylated phosphatidylinositols. The structure of the matrix protein-phosphatidylinositol-(4,5)-bisphosphate [PI(4,5)P(2)] complex was then calculated with HADDOCK software based on the intermolecular nuclear Overhauser enhancement contacts between the ligand and the matrix protein obtained from a (13)C-filtered/(13)C-edited nuclear Overhauser enhancement spectroscopy experiment. PI(4,5)P(2) binding was not strong enough for triggering of the myristoyl-switch. The structural changes of the myristoylated matrix protein were also found to result in a drop in the oligomerization capacity of the protein.
authors.affiliation: Laboratory of NMR Spectroscopy, Institute of Chemical Technology, Prague, Technická 5, 16628 Prague, Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Prchal
authors.forename: Pavel
authors.initials: P
authors.lastname: Srb
authors.forename: Eric
authors.initials: E
authors.lastname: Hunter
authors.forename: Tomáš
authors.initials: T
authors.lastname: Ruml
authors.forename: Richard
authors.initials: R
authors.lastname: Hrabal
mesh_terms: D001665:Binding Sites; D002462:Cell Membrane / Q000378:metabolism*; D016093:Mason-Pfizer monkey virus / Q000737:chemistry*; D009226:Myristates / Q000737:chemistry*; D019906:Nuclear Magnetic Resonance, Biomolecular; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism*; D014763:Viral Matrix Proteins / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D009226:Myristates; D019269:Phosphatidylinositol 4,5-Diphosphate; D014763:Viral Matrix Proteins