9DE5

Structure of full-length HIV TAR RNA bound to HIV Tat RNA-binding domain

9DE5 の概要

• エントリーDOI: 10.2210/pdb9de5/pdb
• 分子名称: RNA (55-MER), Protein Tat, POTASSIUM ION, ... (4 entities in total)
• 機能のキーワード: viral rna, hiv rna, tar rna, rna-protein complex, hiv tat, rna binding protein, rna, rna-transcription complex, rna/transcription
• 由来する生物種: Human immunodeficiency virus 1; 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 76119.22

構造登録者

Bou-Nader, C.,Zhang, J. (登録日: 2024-08-28, 公開日: 2025-03-12, 最終更新日: 2025-03-19)

主引用文献

Bou-Nader, C.,Link, K.A.,Suddala, K.C.,Knutson, J.R.,Zhang, J.
Structures of complete HIV-1 TAR RNA portray a dynamic platform poised for protein binding and structural remodeling.
Nat Commun, 16:2252-2252, 2025

PubMed Abstract: The HIV-1 TAR RNA plays key roles in viral genome architecture, transcription and replication. Previous structural analyses focused on its upper stem loop, which has served as a paradigm to study RNA structural dynamics. However, an imperfectly paired lower stem immediately abuts and stacks with the upper half, both of which are required for efficient HIV replication. Here, we report crystal structures of the full-length HIV-1 TAR which reveal substantial conformational mobility in its three conserved bulges and in its lower stem, which coordinately maintain the structural fluidity of the entire RNA. We find that TAR RNA is a robust inhibitor of PKR, and primarily uses its lower stem to capture and sequester PKR monomers, preventing their dimerization and activation. The lower stem exhibits transient conformational excursions detected by a ligation assay. Time-resolved fluorescence spectroscopy reveals local and global TAR structural remodeling by HIV-1 nucleocapsid, Tat, and PKR. This study portrays the structure, dynamics, and interactions of a complete TAR RNA, uncovers a convergent RNA-based viral strategy to evade innate immunity, and provides avenues to develop antivirals that target a dynamic, multifunctional viral RNA.

PubMed: 40050622
DOI: 10.1038/s41467-025-57519-w

実験手法

X-RAY DIFFRACTION (2.75 Å)