Poster Presentation The 42nd Lorne Conference on Protein Structure and Function 2017

HIV Gag assembly is an exothermic process guided by the initial interaction between nucleic acid and Gag (#245)

Han Tanwar 1 2
  1. Manufacturing, CSIRO, Parkville, VIC, Australia
  2. Medicine, Deakin, Waurn Ponds, VICTORIA, Australia

The HIV-1 Gag precursor protein, Pr55Gag, is the major structural protein that orchestrates the assembly of the virus particles. Although biochemical and biophysical characterization of recombinant Pr55Gag can potentially reveal the fundamental mechanism of HIV assembly, producing sufficient quantity of full length Pr55Gag has been a major limitation for such analyses. We previously reported the production of full-length recombinant Gag using a C-terminus 6xHis tag, and we had since improved our methodology that has resulted in over 10 fold increase of Pr55Gag using a bioreactor-based procedure. We have compared the ability of Pr55Gag and the more widely used Pr50∆p6Gag to oligomerize and to assemble virus-like-particles (VLPs) in an in vitro assay. We found both proteins to have similar capacity to form oligomers in the presence of nucleic acid. We have examined the thermodynamics of HIV Gag assembly using Isothermal Titration Calorimetry (ITC) and demonstrated that the oligomerization and/or the assembly of HIV Gag is an exothermic reaction. A greater amount of energy was released when full length Pr55Gag was used over when Pr50Δp6Gag was used. A significantly lower amount of energy was released when short pieces of nucleic acid (4 nucleotides long) were used to trigger Gag oligomerization. a similarly reduced level of energy release was detected when an HIV Gag capsid dimerization interface mutant was used. Our recombinant protein provides a novel methodology to study HIV assembly, and additional ITC and ultra-structure data will also be presented.