8U3M

The FARFAR-MD-NMR ensemble of an HIV-1 TAR excited state

8U3M の概要

• エントリーDOI: 10.2210/pdb8u3m/pdb
• NMR情報: BMRB: 31106
• 分子名称: The excited state of HIV-1 transactivation response element (31-MER) (1 entity in total)
• 機能のキーワード: hiv-1 transactivation response element, rna
• 由来する生物種: Human immunodeficiency virus 1
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 9918.90

構造登録者

Geng, A.,Ganser, L.,Roy, R.,Shi, H.,Pratihar, S.,Case, D.A.,Al-Hashimi, H.M. (登録日: 2023-09-07, 公開日: 2023-10-04, 最終更新日: 2024-05-15)

主引用文献

Geng, A.,Ganser, L.,Roy, R.,Shi, H.,Pratihar, S.,Case, D.A.,Al-Hashimi, H.M.
An RNA excited conformational state at atomic resolution.
Nat Commun, 14:8432-8432, 2023

PubMed Abstract: Sparse and short-lived excited RNA conformational states are essential players in cell physiology, disease, and therapeutic development, yet determining their 3D structures remains challenging. Combining mutagenesis, NMR spectroscopy, and computational modeling, we determined the 3D structural ensemble formed by a short-lived (lifetime ~2.1 ms) lowly-populated (~0.4%) conformational state in HIV-1 TAR RNA. Through a strand register shift, the excited conformational state completely remodels the 3D structure of the ground state (RMSD from the ground state = 7.2 ± 0.9 Å), forming a surprisingly more ordered conformational ensemble rich in non-canonical mismatches. The structure impedes the formation of the motifs recognized by Tat and the super elongation complex, explaining why this alternative TAR conformation cannot activate HIV-1 transcription. The ability to determine the 3D structures of fleeting RNA states using the presented methodology holds great promise for our understanding of RNA biology, disease mechanisms, and the development of RNA-targeting therapeutics.

PubMed: 38114465
DOI: 10.1038/s41467-023-43673-6

実験手法

SOLUTION NMR