Work

Insights About the Structure and Recognition Mechanism of the Rev Response Element of HIV-1 Revealed by FRET-monitored Mutagenesis and Modeling

Year: 2025

Type: article

Abstract: The complex between several monomers of the HIV-1 Rev protein and the Rev Response Element (RRE) in the viral RNA allows nuclear export of unspliced or singly-spliced viral transcripts, an essential step in the virus cycle that is not targeted by any of the currently marketed antiretroviral treatments. The RRE adopts a multi-domain structure whose three-dimensional details are currently unknown at atomic resolution. In order to shed light on RRE structure and on the mechanism of RRE-Rev complex assembly, we set up a method based on fluorescence resonance energy transfer (FRET) that has allowed us to measure RRE interdomain distance as a function of solution conditions and changes in helix length and junction nucleotides. By combining this information with all-atom ensemble modeling, comparative sequence analyses and electrophoretic band-shift assays assessing Rev association, we clarify the roles of helices and junctions on the spatial organization of RRE domains and RRE-Rev complex formation and propose an all-atom model of RRE structure consistent with the available evidence.

Source: Journal of Molecular Biology

DOI: 10.1016/j.jmb.2025.169451

Authors: Mateusz P. Szewczyk, Saurabh Loharch, Sergio López-Núñez, José Gallego

Institution: Valencia Catholic University Saint Vincent Martyr

Language: English

Topic: HIV Research and Treatment

Subfield: Virology

Field: Immunology and Microbiology

Domain: Life Sciences

Open Access status: hybrid

Estimated APC paid: $4,730

Funders: Generalitat Valenciana, Ministerio de Ciencia e Innovación, European Regional Development Fund