Journal Article

Structure of HIV-1 RRE stem-loop II identifies two conformational states of the high-affinity Rev binding site

Slaton, Michael, Tipo, Jerricho, Gottipati, Keerthi, Gonzalez-Gutierrez, Giovanni, Choi, Kyung H.

2024

Overview

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. HIV relies on the RRE RNA interaction with Rev protein for nuclear export of viral mRNAs. The structure of the high-affinity Rev binding site in RRE in two conformations suggests a mechanism for initial Rev binding and oligomerization onto RRE.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 60 APPLIED LIFE SCIENCES / 631/326/596/1787 / 631/45/500 / 631/535/1266 / 82/29 / Affinity / Base Sequence / Binding sites / Crystal structure / Genes, env / Grooves / HIV / HIV Infections - virology / HIV-1 - chemistry / HIV-1 - genetics / Human immunodeficiency virus / Humanities and Social Sciences / Humans / multidisciplinary / Nuclear transport / Nucleic Acid Conformation / Nucleotide Motifs / Oligomerization / Protein transport / Proteins / Retrovirus / Rev protein / RNA / RNA, Viral - chemistry / RNA-protein interactions / Science / Science & Technology / Science (multidisciplinary) / X-ray crystallography