NMR Structure of the Myristylated Feline Immunodeficiency Virus Matrix Protein [unknown]

L.A. Brown, C. Cox, R.J. Button, J. Baptiste, K. Bahlow, V. Spurrier, B.G. Luttge, L. Kuo, E.O. Freed, M.F. Summers, J. Kyser, H.R. Summers
2015 unpublished
Membrane 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
more » ... lational myristylation was facilitated by mutation of two amino acids near the amino-terminus of the protein (Q5A/G6S; myrMA Q5A/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, OPEN ACCESS Viruses 2015, 7 2211 FIV hijacks the PI(4,5)P2 cellular signaling system to direct intracellular Gag trafficking during virus assembly.
doi:10.2210/pdb2n1r/pdb fatcat:2fqk6vm22ng45jqxgjlgr7qaje