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Viruses 2015, 7(5), 2210-2229; doi:10.3390/v7052210

NMR Structure of the Myristylated Feline Immunodeficiency Virus Matrix Protein

1
Howard Hughes Medical Institute, University of Maryland Baltimore County, 1000 Hilltop Circle, Baltimore, MD 21250, USA
2
Virus-Cell Interaction Section, HIV Drug Resistance Program, National Cancer Institute at Frederick, Frederick, MD 21702-1201, USA
*
Authors to whom correspondence should be addressed.
Academic Editor: Andrew Mehle
Received: 5 March 2015 / Revised: 30 March 2015 / Accepted: 21 April 2015 / Published: 30 April 2015
(This article belongs to the Section Animal Viruses)
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Abstract

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; 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
Keywords: Feline immunodeficiency virus (FIV); nuclear magnetic resonance (NMR); protein structure; retrovirus assembly; membrane targeting; phosphatidylinositol-4,5-bisphosphate [PI(4,5)-P2; PIP2] Feline immunodeficiency virus (FIV); nuclear magnetic resonance (NMR); protein structure; retrovirus assembly; membrane targeting; phosphatidylinositol-4,5-bisphosphate [PI(4,5)-P2; PIP2]
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

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.

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