Functional Equivalence of Retroviral MA Domains in Facilitating Psi RNA Binding Specificity by Gag
AbstractRetroviruses specifically package full-length, dimeric genomic RNA (gRNA) even in the presence of a vast excess of cellular RNA. The “psi” (Ψ) element within the 5′-untranslated region (5′UTR) of gRNA is critical for packaging through interaction with the nucleocapsid (NC) domain of Gag. However, in vitro Gag binding affinity for Ψ versus non-Ψ RNAs is not significantly different. Previous salt-titration binding assays revealed that human immunodeficiency virus type 1 (HIV-1) Gag bound to Ψ RNA with high specificity and relatively few charge interactions, whereas binding to non-Ψ RNA was less specific and involved more electrostatic interactions. The NC domain was critical for specific Ψ binding, but surprisingly, a Gag mutant lacking the matrix (MA) domain was less effective at discriminating Ψ from non-Ψ RNA. We now find that Rous sarcoma virus (RSV) Gag also effectively discriminates RSV Ψ from non-Ψ RNA in a MA-dependent manner. Interestingly, Gag chimeras, wherein the HIV-1 and RSV MA domains were swapped, maintained high binding specificity to cognate Ψ RNAs. Using Ψ RNA mutant constructs, determinants responsible for promoting high Gag binding specificity were identified in both systems. Taken together, these studies reveal the functional equivalence of HIV-1 and RSV MA domains in facilitating Ψ RNA selectivity by Gag, as well as Ψ elements that promote this selectivity. View Full-Text
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Rye-McCurdy, T.; Olson, E.D.; Liu, S.; Binkley, C.; Reyes, J.-P.; Thompson, B.R.; Flanagan, J.M.; Parent, L.J.; Musier-Forsyth, K. Functional Equivalence of Retroviral MA Domains in Facilitating Psi RNA Binding Specificity by Gag. Viruses 2016, 8, 256.
Rye-McCurdy T, Olson ED, Liu S, Binkley C, Reyes J-P, Thompson BR, Flanagan JM, Parent LJ, Musier-Forsyth K. Functional Equivalence of Retroviral MA Domains in Facilitating Psi RNA Binding Specificity by Gag. Viruses. 2016; 8(9):256.Chicago/Turabian Style
Rye-McCurdy, Tiffiny; Olson, Erik D.; Liu, Shuohui; Binkley, Christiana; Reyes, Joshua-Paolo; Thompson, Brian R.; Flanagan, John M.; Parent, Leslie J.; Musier-Forsyth, Karin. 2016. "Functional Equivalence of Retroviral MA Domains in Facilitating Psi RNA Binding Specificity by Gag." Viruses 8, no. 9: 256.
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