9E7E

Crystal structure of HIV-1 RRE SLII A31CG39C mutant in complex with Fab BL3-6

9E7E の概要

• エントリーDOI: 10.2210/pdb9e7e/pdb
• 分子名称: BL3-6 Fab heavy chain, BL3-6 Fab light chain, Rev Response Element SLII A31C/G39C, ... (4 entities in total)
• 機能のキーワード: hiv-1, replication, fab, chaperone, rev response element, rna
• 由来する生物種: Homo sapiens; 詳細
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 285437.46

構造登録者

Ojha, M.,Koirala, D. (登録日: 2024-11-01, 公開日: 2025-05-28, 最終更新日: 2026-06-10)

主引用文献

Ojha, M.,Hudson, L.,Photenhauer, A.,Zang, T.,Lerew, L.,Ekesan, S.,Daniels, J.,Nguyen, M.,Paudyal, H.,York, D.M.,Ohi, M.D.,Marchant, J.,Bieniasz, P.D.,Koirala, D.
Mutation-driven RRE stem-loop II conformational change induces HIV-1 nuclear export dysfunction.
Nucleic Acids Res., 53:-, 2025

PubMed Abstract: The Rev response element (RRE) forms an oligomeric complex with the viral protein Rev to facilitate the nuclear export of intron-retaining viral RNAs during the late phase of HIV-1 (human immunodeficiency virus type 1) infection. However, the structures and mechanisms underlying this process remain largely unknown. Here, we determined the crystal structure of the HIV-1 RRE stem-loop II (SLII), revealing a unique three-way junction architecture in which the base stem (IIa) bifurcates into the stem-loops (IIb and IIc) to compose Rev binding sites. The crystal structures of various SLII mutants demonstrated that while some mutants retain the same "compact" fold as the wild type, other single-nucleotide mutants induce drastic conformational changes, forming an "extended" SLII structure. Through in vitro Rev binding assays and Rev activity measurements in HIV-1-infected cells using structure-guided SLII mutants designed to favor specific conformers, we showed that while the compact fold represents a functional SLII, the alternative extended conformation inhibits Rev binding and oligomerization and consequently stimulates HIV-1 RNA nuclear export dysfunction. The propensity of SLII to adopt multiple conformations as captured in crystal structures and their influence on Rev oligomerization illuminate emerging perspectives on RRE structural plasticity-based regulation of HIV-1 nuclear export and provide opportunities for developing anti-HIV drugs targeting specific RRE conformations.

PubMed: 40613716
DOI: 10.1093/nar/gkaf583

実験手法

X-RAY DIFFRACTION (2.75 Å)