7OQH

CryoEM structure of the transcription termination factor Rho from Mycobacterium tuberculosis

7OQH の概要

• エントリーDOI: 10.2210/pdb7oqh/pdb
• EMDBエントリー: 12701
• 分子名称: Transcription termination factor Rho, ADENOSINE-5'-TRIPHOSPHATE, MAGNESIUM ION (3 entities in total)
• 機能のキーワード: transcription termination factor, rna helicase, atp-dependent, molecular motor, transcription
• 由来する生物種: Mycobacterium tuberculosis
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 407340.83

構造登録者

Saridakis, E.,Vishwakarma, R.,Lai Kee Him, J.,Martin, K.,Simon, I.,Cohen-Gonsaud, M.,Coste, F.,Bron, P.,Margeat, E.,Boudvillain, M. (登録日: 2021-06-03, 公開日: 2022-02-09, 最終更新日: 2024-07-17)

主引用文献

Saridakis, E.,Vishwakarma, R.,Lai-Kee-Him, J.,Martin, K.,Simon, I.,Cohen-Gonsaud, M.,Coste, F.,Bron, P.,Margeat, E.,Boudvillain, M.
Cryo-EM structure of transcription termination factor Rho from Mycobacterium tuberculosis reveals bicyclomycin resistance mechanism.
Commun Biol, 5:120-120, 2022

PubMed Abstract: The bacterial Rho factor is a ring-shaped motor triggering genome-wide transcription termination and R-loop dissociation. Rho is essential in many species, including in Mycobacterium tuberculosis where rho gene inactivation leads to rapid death. Yet, the M. tuberculosis Rho [Rho] factor displays poor NTPase and helicase activities, and resistance to the natural Rho inhibitor bicyclomycin [BCM] that remain unexplained. To address these issues, we solved the cryo-EM structure of Rho at 3.3 Å resolution. The Rho hexamer is poised into a pre-catalytic, open-ring state wherein specific contacts stabilize ATP in intersubunit ATPase pockets, thereby explaining the cofactor preference of Rho. We reveal a leucine-to-methionine substitution that creates a steric bulk in BCM binding cavities near the positions of ATP γ-phosphates, and confers resistance to BCM at the expense of motor efficiency. Our work contributes to explain the unusual features of Rho and provides a framework for future antibiotic development.

PubMed: 35140348
DOI: 10.1038/s42003-022-03069-6

実験手法

ELECTRON MICROSCOPY (3.32 Å)