Structure of HIV-1 RRE stem-loop II identifies two conformational states of the high-affinity Rev binding site.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
17 May 2024
17 May 2024
Historique:
received:
17
11
2023
accepted:
22
04
2024
medline:
18
5
2024
pubmed:
18
5
2024
entrez:
17
5
2024
Statut:
epublish
Résumé
During HIV infection, specific RNA-protein interaction between the Rev response element (RRE) and viral Rev protein is required for nuclear export of intron-containing viral mRNA transcripts. Rev initially binds the high-affinity site in stem-loop II, which promotes oligomerization of additional Rev proteins on RRE. Here, we present the crystal structure of RRE stem-loop II in distinct closed and open conformations. The high-affinity Rev-binding site is located within the three-way junction rather than the predicted stem IIB. The closed and open conformers differ in their non-canonical interactions within the three-way junction, and only the open conformation has the widened major groove conducive to initial Rev interaction. Rev binding assays show that RRE stem-loop II has high- and low-affinity binding sites, each of which binds a Rev dimer. We propose a binding model, wherein Rev-binding sites on RRE are sequentially created through structural rearrangements induced by Rev-RRE interactions.
Identifiants
pubmed: 38760344
doi: 10.1038/s41467-024-48162-y
pii: 10.1038/s41467-024-48162-y
doi:
Substances chimiques
rev protein, Human Immunodeficiency Virus-1
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
4198Subventions
Organisme : University of Texas Medical Branch (University of Texas Medical Branch at Galveston)
ID : Kempner pre-doctoral fellowship
Informations de copyright
© 2024. The Author(s).
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