NMR structure of the myristylated feline immunodeficiency virus matrix protein. Academic Article uri icon

Overview

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.

authors

  • Brown, Lola
  • 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

publication date

  • April 30, 2015

Research

keywords

  • Immunodeficiency Virus, Feline
  • Viral Matrix Proteins

Identity

PubMed Central ID

  • PMC4452903

Scopus Document Identifier

  • 84929336741

Digital Object Identifier (DOI)

  • 10.1016/S0167-4889(99)00075-0

PubMed ID

  • 25941825

Additional Document Info

volume

  • 7

issue

  • 5