7OQH

CryoEM structure of the transcription termination factor Rho from Mycobacterium tuberculosis

Summary for 7OQH

• Entry DOI: 10.2210/pdb7oqh/pdb
• EMDB information: 12701
• Descriptor: Transcription termination factor Rho, ADENOSINE-5'-TRIPHOSPHATE, MAGNESIUM ION (3 entities in total)
• Functional Keywords: transcription termination factor, rna helicase, atp-dependent, molecular motor, transcription
• Biological source: Mycobacterium tuberculosis
• Total number of polymer chains: 6
• Total formula weight: 407340.83

Authors

Saridakis, E.,Vishwakarma, R.,Lai Kee Him, J.,Martin, K.,Simon, I.,Cohen-Gonsaud, M.,Coste, F.,Bron, P.,Margeat, E.,Boudvillain, M. (deposition date: 2021-06-03, release date: 2022-02-09, Last modification date: 2024-07-17)

Primary citation

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

Experimental method

ELECTRON MICROSCOPY (3.32 Å)