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-Structure paper
タイトル | Cryo-EM structure of transcription termination factor Rho from Mycobacterium tuberculosis reveals bicyclomycin resistance mechanism. |
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ジャーナル・号・ページ | Commun Biol, Vol. 5, Issue 1, Page 120, Year 2022 |
掲載日 | 2022年2月9日 |
著者 | Emmanuel Saridakis / Rishi Vishwakarma / Josephine Lai-Kee-Him / Kevin Martin / Isabelle Simon / Martin Cohen-Gonsaud / Franck Coste / Patrick Bron / Emmanuel Margeat / Marc Boudvillain / |
PubMed 要旨 | 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 ...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. |
リンク | Commun Biol / PubMed:35140348 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.32 Å |
構造データ | EMDB-12701: CryoEM structure of the transcription termination factor Rho from Mycrobacterium Tuberculosis |
化合物 | ChemComp-ATP: ChemComp-MG: |
由来 |
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キーワード | TRANSCRIPTION (転写 (生物学)) / transcription termination factor / RNA helicase (ヘリカーゼ) / ATP-dependent / molecular motor (分子モーター) |