8U3M

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

Summary for 8U3M

• Entry DOI: 10.2210/pdb8u3m/pdb
• NMR Information: BMRB: 31106
• Descriptor: The excited state of HIV-1 transactivation response element (31-MER) (1 entity in total)
• Functional Keywords: hiv-1 transactivation response element, rna
• Biological source: Human immunodeficiency virus 1
• Total number of polymer chains: 1
• Total formula weight: 9918.90

Authors

Geng, A.,Ganser, L.,Roy, R.,Shi, H.,Pratihar, S.,Case, D.A.,Al-Hashimi, H.M. (deposition date: 2023-09-07, release date: 2023-10-04, Last modification date: 2024-05-15)

Primary citation

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

Experimental method

SOLUTION NMR