The Structure of Myristoylated Mason-Pfizer Monkey Virus Matrix Protein and the Role of Phosphatidylinositol-(4,5)-Bisphosphate in Its Membrane Binding |
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| Authors: | Jan Prchal Pavel Srb Eric Hunter Tomáš Ruml Richard Hrabal |
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| Affiliation: | 1. Laboratory of NMR Spectroscopy, Institute of Chemical Technology, Prague, Technická 5, 16628 Prague, Czech Republic;2. Department of Biochemistry and Microbiology, Institute of Chemical Technology, Prague, Technická 5, 16628 Prague, Czech Republic;3. Department of Low Temperature Physics, Faculty of Mathematics and Physics, Charles University, V Hole?ovi?kách 2, 18000 Prague, Czech Republic;4. Emory Vaccine Center, 954 Gatewood Road, Atlanta, GA 30329, USA;3. Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267 and;4. Department of Cell and Molecular Physiology, Stritch School of Medicine, Loyola University Chicago, Maywood, Illinois 60153;3. Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, Pennsylvania 16802;8. Department of Chemistry, Pennsylvania State University, University Park, Pennsylvania 16802,;4. Graduate School of Biomedical Science and Engineering, Hanyang University, 222 Wangsimri-ro, Seongdong-gu, Seoul, 133-791, Korea,;5. Department of Chemistry, Saint Francis University, Loretto, Pennsylvania 15940,;6. Department of Microbial Pathogenesis, Yale School of Medicine, New Haven, Connecticut 06536, and;12. Department of Pharmaceutical Science and Research, Marshall University School of Pharmacy, Huntington, West Virginia 25755;3. Medical and Research Services, James A. Haley Veterans Medical Center, Tampa, Florida 33612 and;4. Division of Endocrinology and Metabolism, Department of Internal Medicine, University of South Florida College of Medicine, Tampa, Florida 33612;1. Department of Microbiology, Institute of Health Biosciences, The University of Tokushima Graduate School, 3-18-15 Kuramoto, Tokushima 770-8503, Japan;2. Japanese Foundation for AIDS Prevention, Chiyoda-ku, Tokyo 101-0061, Japan;3. W. M. Keck Laboratory for Structural Biology, University of Maryland Institute for Bioscience and Biotechnology Research, Rockville, Maryland 20850;4. Department of Chemistry and Biochemistry, University of Maryland, College Park, Maryland 20742;5. Department of Urology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287;6. Shakti BioResearch, Woodbridge, Connecticut 06525;1. Graduate School of Biomedical Sciences, Rowan University, Stratford, NJ 08084, USA;2. School of Osteopathic Medicine, Rowan University, Stratford, NJ 08084, USA |
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| 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 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. |
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