NMR Structure of the Myristylated Feline Immunodeficiency Virus Matrix Protein
AbstractMembrane targeting by the Gag proteins of the human immunodeficiency viruses (HIV types-1 and -2) is mediated by Gag’s N-terminally myristylated matrix (MA) domain and is dependent on cellular phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2]. To determine if other lentiviruses employ a similar membrane targeting mechanism, we initiated studies of the feline immunodeficiency virus (FIV), a widespread feline pathogen with potential utility for development of human therapeutics. Bacterial co-translational myristylation was facilitated by mutation of two amino acids near the amino-terminus of the protein (Q5A/G6S; myrMAQ5A/G6S). These substitutions did not affect virus assembly or release from transfected cells. NMR studies revealed that the myristyl group is buried within a hydrophobic pocket in a manner that is structurally similar to that observed for the myristylated HIV-1 protein. Comparisons with a recent crystal structure of the unmyristylated FIV protein [myr(-)MA] indicate that only small changes in helix orientation are required to accommodate the sequestered myr group. Depletion of PI(4,5)P2 from the plasma membrane of FIV-infected CRFK cells inhibited production of FIV particles, indicating that, like HIV, FIV hijacks the PI(4,5)P2 cellular signaling system to direct intracellular Gag trafficking during virus assembly. View Full-Text
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Brown, L.A.; Cox, C.; Baptiste, J.; Summers, H.; Button, R.; Bahlow, K.; Spurrier, V.; Kyser, J.; Luttge, B.G.; Kuo, L.; Freed, E.O.; Summers, M.F. NMR Structure of the Myristylated Feline Immunodeficiency Virus Matrix Protein. Viruses 2015, 7, 2210-2229.
Brown LA, Cox C, Baptiste J, Summers H, Button R, Bahlow K, Spurrier V, Kyser J, Luttge BG, Kuo L, Freed EO, Summers MF. NMR Structure of the Myristylated Feline Immunodeficiency Virus Matrix Protein. Viruses. 2015; 7(5):2210-2229.Chicago/Turabian Style
Brown, Lola A.; Cox, Cassiah; Baptiste, Janae; Summers, Holly; Button, Ryan; Bahlow, Kennedy; Spurrier, Vaughn; Kyser, Jenna; Luttge, Benjamin G.; Kuo, Lillian; Freed, Eric O.; Summers, Michael F. 2015. "NMR Structure of the Myristylated Feline Immunodeficiency Virus Matrix Protein." Viruses 7, no. 5: 2210-2229.