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Article Abstract
HIV-1 particle assembly depends critically on multiple proteolytic cleavages of viral polyproteins by the viral protease, PR. PR is translated as part of the Gag-Pro-Pol polyprotein, which undergoes autoproteolysis to liberate active, dimeric PR during virus particle maturation. Gag-Pro-Pol is produced via an infrequent -1 frameshifting event in ribosomes translating full length genomic RNA as Gag mRNA. Here, we study the cotranslational folding and autoproteolytic processing of frameshifted transframe-protease-reverse transcriptase (TF-PR-RT) constructs by translation. We demonstrate partial cotranslational folding of ribosome-bound PR at its conserved α-helix near the C terminus. Unexpectedly, we find that the initial dimerization of TF-PR-RT involves ribosome-bound nascent chains that are then not further cleaved. Moreover, only ribosome-bound nascent chains are substrates for PR-catalyzed processing. These observations are consistent with a model for virion assembly in which dimerization of a subset of Pro-Pol precursors leads to cleavage of PR monomers that then carry out the bulk of the proteolytic processing needed for virion maturation and infectivity.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC12407942 | PMC |
| http://dx.doi.org/10.1101/2025.08.27.672612 | DOI Listing |
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