Structure of HIV-1 RRE stem-loop II identifies two conformational states of the high-affinity Rev binding site.
Nat Commun
; 15(1): 4198, 2024 May 17.
Article
in En
| MEDLINE
| ID: mdl-38760344
ABSTRACT
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Genes, env
/
HIV-1
Limits:
Humans
Language:
En
Journal:
Nat Commun
/
Nature communications
Journal subject:
BIOLOGIA
/
CIENCIA
Year:
2024
Type:
Article
Affiliation country:
United States