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9E7V

Off-pathway Mycobacterium tuberculosis transcription initiation promoter complex (RNA Polymerase with Sigma-A, CarD, and RbpA)

Summary for 9E7V
Entry DOI10.2210/pdb9e7v/pdb
EMDB information47692
DescriptorDNA-directed RNA polymerase subunit alpha, PYROPHOSPHATE 2-, ZINC ION, ... (12 entities in total)
Functional Keywordspromoter escape, transcription, transcription-dna complex, transcription/dna
Biological sourceMycobacterium tuberculosis
More
Total number of polymer chains10
Total formula weight550443.63
Authors
Brewer, J.J.,Campbell, E.A.,Darst, S.A. (deposition date: 2024-11-04, release date: 2025-10-01, Last modification date: 2025-12-03)
Primary citationBrewer, J.,Delbeau, M.,Zoullas, W.B.,Darst, S.A.,Campbell, E.A.
Structural Insights into De Novo Promoter Escape by Mycobacterium tuberculosis RNA Polymerase.
Nat Commun, 16:9990-9990, 2025
Cited by
PubMed Abstract: Transcription in bacteria is a multi-step process. In the first step, contacts between RNA polymerase and the promoter DNA must be established for transcription initiation to begin, but then these contacts must be broken for the enzyme to transition into the elongation phase. Single-molecule and biochemical observations report that promoter escape is a highly regulated and sometimes rate-limiting step in the transcription cycle; however, the structural mechanisms of promoter escape remain obscure. Promoter escape also serves as the target for the clinically important antibiotic rifampicin, used to treat tuberculosis. Here, we present seven distinct intermediates showing the structural details of M. tuberculosis RNA polymerase initial transcribing complexes and promoter escape, using a de novo cryo-electron microscopy approach. We describe the structural rearrangements that RNA polymerase undergoes to clear the promoter, including those required to release the initiation factor, σ, providing a structural account for decades of biochemical observations. These structures and supporting biochemistry provide a model of promoter escape, a universal step in the transcription cycle, with conformations that may be used to develop Rifampicin alternatives.
PubMed: 41233305
DOI: 10.1038/s41467-025-64941-7
PDB entries with the same primary citation
Experimental method
ELECTRON MICROSCOPY (3.4 Å)
Structure validation

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PDB entries from 2026-01-07

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