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| Title | Structures of transcription complexes reveal how ToxR and TcpP recruit the RNA polymerase and activate virulence genes. |
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| Journal, issue, pages | Sci Adv, Vol. 12, Issue 3, Page eadx9680, Year 2026 |
| Publish date | Jan 16, 2026 |
Authors | Adrià Alcaide-Jiménez / Albert Canals / Florence Baudin / Cristina Machón / Montserrat Fàbrega-Ferrer / Olga Bantysh / Rosa Pérez-Luque / Brice Murciano / Ali A Mohammad / Michael J Rowse / Joseph M Ferracciolo / Eric S Krukonis / Christoph W Müller / Miquel Coll / ![]() |
| PubMed Abstract | Activation of virulence in , the etiological agent of cholera disease, is mediated by two transmembrane one-component signal-transduction proteins, ToxR and TcpP, which are also transcription factors. ...Activation of virulence in , the etiological agent of cholera disease, is mediated by two transmembrane one-component signal-transduction proteins, ToxR and TcpP, which are also transcription factors. Using cryo-electron microscopy, we have solved five structures of the and transcription activation complexes, including the RNA polymerase (RNAP) holoenzyme, promoter DNAs, transcribed RNA, and their corresponding transcription factors, ToxR or TcpP and ToxR-TcpP, respectively. Activation is achieved through the interaction of ToxR or TcpP with the α-C-terminal repeat domain of RNAP where a single residue of the activator, a phenylalanine, appears to be the most critical contact, as confirmed by mutagenesis. No interactions of the transcription factors were observed with other subunits of the RNAP, i.e., the σ subunit as it occurs in the structurally related PhoB family of two-component transcription factors. The structures, and their comparison with our previously solved DNA promoter-ToxR x-ray structures, unveil the molecular mechanism of cholera virulence gene activation. |
External links | Sci Adv / PubMed:41533787 / PubMed Central |
| Methods | EM (single particle) |
| Resolution | 2.6 - 7.2 Å |
| Structure data | EMDB-51273, PDB-9gdo: EMDB-51274, PDB-9gdp: EMDB-51275, PDB-9gdq: EMDB-51276, PDB-9gdr: EMDB-51277, PDB-9gds: ![]() EMDB-51278: Cryo-EM structure of Vibrio cholerae RNA polymerase dimer with ToxR and TcpP transcription factors and a toxT promoter DNA fragment ![]() EMDB-51774: Consensus map of the cryo-EM structure of Vibrio cholerae RNA polymerase Transcription Activation Complex with ToxR transcription factor and bound to an ompU promoter DNA fragment ![]() EMDB-51775: Focused map #1 of the cryo-EM structure of Vibrio cholerae RNA polymerase Transcription Activation Complex with ToxR transcription factor and bound to an ompU promoter DNA fragment ![]() EMDB-51776: Focused map #2 of the cryo-EM structure of Vibrio cholerae RNA polymerase Transcription Activation Complex with ToxR transcription factor and bound to an ompU promoter DNA fragment ![]() EMDB-51948: Consensus map of the cryo-EM structure of Vibrio cholerae RNA polymerase Transcription Activation Complex with TcpP transcription factor and bound to a toxT promoter DNA fragment ![]() EMDB-51949: Focused map #1 of the cryo-EM structure of Vibrio cholerae RNA polymerase Transcription Activation Complex with TcpP transcription factor and bound to a toxT promoter DNA fragment ![]() EMDB-51950: Focused map #2 of the cryo-EM structure of Vibrio cholerae RNA polymerase Transcription Activation Complex with TcpP transcription factor and bound to a toxT promoter DNA fragment ![]() EMDB-51955: Consensus map of the cryo-EM structure of Vibrio cholerae RNA polymerase Transcription Activation Complex with ToxR and TcpP transcription factors and bound to a toxT promoter DNA fragment ![]() EMDB-51956: Focused map #1 of the cryo-EM structure of Vibrio cholerae RNA polymerase Transcription Activation Complex with ToxR and TcpP transcription factors and bound to a toxT promoter DNA fragment ![]() EMDB-51958: Focused map #2 of the cryo-EM structure of Vibrio cholerae RNA polymerase Transcription Activation Complex with ToxR and TcpP transcription factors and bound to a toxT promoter DNA fragment |
| Chemicals | ![]() ChemComp-MG: ![]() ChemComp-ZN: |
| Source |
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Keywords | TRANSCRIPTION / RNA polymerase / Open promoter complex / ompU / Vibrio cholerae / Transcription Activation Complex / toxT / TcpP / ToxR |
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vibrio cholerae o395 (bacteria)
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