NMR Structure of the Myristylated Feline Immunodeficiency Virus Matrix Protein

Viruses

Lola A. Brown²  Cassiah Cox²  Janae Baptiste²  Holly Summers²  Ryan Button²  Kennedy Bahlow²  Vaughn Spurrier²  Jenna Kyser²  Benjamin G. Luttge¹  Lillian Kuo¹  Eric O. Freed¹  Michael F. Summers² 

[1] Virus-Cell Interaction Section, HIV Drug Resistance Program, National Cancer Institute at Frederick, Frederick, MD 21702-1201, USA; E-Mails:;Howard Hughes Medical Institute, University of Maryland Baltimore County, 1000 Hilltop Circle, Baltimore, MD 21250, USA; E-Mails:

关键词: Feline immunodeficiency virus (FIV);    nuclear magnetic resonance (NMR);    protein structure;    retrovirus assembly;    membrane targeting;    phosphatidylinositol-4;    5-bisphosphate [PI(4;    5)-P₂;    PIP₂];   

DOI  :  10.3390/v7052210

来源: mdpi

【 摘 要 】

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 co-translational 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, FIV hijacks the PI(4,5)P₂ cellular signaling system to direct intracellular Gag trafficking during virus assembly.

【 授权许可】

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© 2015 by the authors; licensee MDPI, Basel, Switzerland.