UMMS Affiliation

Department of Microbiology and Physiological Systems

Publication Date

2021-09-14

Document Type

Article

Disciplines

Amino Acids, Peptides, and Proteins | Biochemistry | Biophysics | Nucleic Acids, Nucleotides, and Nucleosides | Structural Biology | Virology

Abstract

During HIV-1 assembly, the viral Gag polyprotein specifically selects the dimeric RNA genome for packaging into new virions. The 5' untranslated region (5'UTR) of the dimeric genome may adopt a conformation that is optimal for recognition by Gag. Further conformational rearrangement of the 5'UTR, promoted by the nucleocapsid (NC) domain of Gag, is predicted during virus maturation. Two 5'UTR dimer conformations, the kissing dimer (KD) and the extended dimer (ED), have been identified in vitro, which differ in the extent of intermolecular basepairing. Whether 5'UTRs from different HIV-1 strains with distinct sequences have access to the same dimer conformations has not been determined. Here, we applied fluorescence cross-correlation spectroscopy and single-molecule Forster resonance energy transfer imaging to demonstrate that 5'UTRs from two different HIV-1 subtypes form (KDs) with divergent stabilities. We further show that both 5'UTRs convert to a stable dimer in the presence of the viral NC protein, adopting a conformation consistent with extensive intermolecular contacts. These results support a unified model in which the genomes of diverse HIV-1 strains adopt an ED conformation.

Keywords

HIV-1, conformation

Rights and Permissions

Copyright 2021 Biophysical Society. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

DOI of Published Version

10.1016/j.bpj.2021.09.017

Source

Blakemore RJ, Burnett C, Swanson C, Kharytonchyk S, Telesnitsky A, Munro JB. Stability and conformation of the dimeric HIV-1 genomic RNA 5'UTR. Biophys J. 2021 Nov 2;120(21):4874-4890. doi: 10.1016/j.bpj.2021.09.017. Epub 2021 Sep 14. PMID: 34529947; PMCID: PMC8595565. Link to article on publisher's site

Journal/Book/Conference Title

Biophysical journal

Related Resources

Link to Article in PubMed

PubMed ID

34529947

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

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