The Structure of Myristoylated Mason-Pfizer Monkey Virus Matrix Protein and the Role of Phosphatidylinositol-(4,5)-Bisphosphate in Its Membrane Binding

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 C8 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 31P 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)P2] 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 13C-filtered/13C-edited nuclear Overhauser enhancement spectroscopy experiment. PI(4,5)P2 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.