The thermodynamics of Pr55Gag-RNA interaction regulate the assembly of HIV
Tanwar, Hanumantsingh, Khoo, Keith K., Garvey, Megan, Waddington, Lynne, Leis, Andrew, Hijnen, Marcel, Velkov, Tony, Dumsday, Geoff J., McKinstry, William J. and Mak, Johnson 2017, The thermodynamics of Pr55Gag-RNA interaction regulate the assembly of HIV, PLoS pathogens, vol. 13, no. 2, pp. 1-24, doi: 10.0.5.91/journal.ppat.1006221.
The interactions that occur during HIV Pr55Gag oligomerization and genomic RNA packagingare essential elements that facilitate HIV assembly. However, mechanistic details ofthese interactions are not clearly defined. Here, we overcome previous limitations in producinglarge quantities of full-length recombinant Pr55Gag that is required for isothermal titrationcalorimetry (ITC) studies, and we have revealed the thermodynamic properties of HIVassembly for the first time. Thermodynamic analysis showed that the binding between RNAand HIV Pr55Gag is an energetically favourable reaction (ΔG<0) that is further enhanced bythe oligomerization of Pr55Gag. The change in enthalpy (ΔH) widens sequentially from: (1)Pr55Gag-Psi RNA binding during HIV genome selection; to (2) Pr55Gag-Guanosine Uridine(GU)-containing RNA binding in cytoplasm/plasma membrane; and then to (3) Pr55Gag-Adenosine(A)-containing RNA binding in immature HIV. These data imply the stepwiseincrements of heat being released during HIV biogenesis may help to facilitate the processof viral assembly. By mimicking the interactions between A-containing RNA and oligomericPr55Gag in immature HIV, it was noted that a p6 domain truncated Pr50Gag Δp6 is less efficientthan full-length Pr55Gag in this thermodynamic process. These data suggest a potentialunknown role of p6 in Pr55Gag-Pr55Gag oligomerization and/or Pr55Gag-RNA interaction duringHIV assembly. Our data provide direct evidence on how nucleic acid sequences and theoligomeric state of Pr55Gag regulate HIV assembly.
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