Protein science, 2024-06, Vol.33 (6), p.e5012-n/a
2024
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- Autor(en) / Beteiligte
- Titel
- Structural and functional insights into transcription activation of the essential LysR‐type transcriptional regulators
- Ist Teil von
- Protein science, 2024-06, Vol.33 (6), p.e5012-n/a
- Ort / Verlag
- Hoboken, USA: John Wiley & Sons, Inc
- Erscheinungsjahr
- 2024
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- The enormous LysR‐type transcriptional regulators (LTTRs), which are diversely distributed amongst prokaryotes, play crucial roles in transcription regulation of genes involved in basic metabolic pathways, virulence and stress resistance. However, the precise transcription activation mechanism of these genes by LTTRs remains to be explored. Here, we determine the cryo‐EM structure of a LTTR‐dependent transcription activation complex comprising of Escherichia coli RNA polymerase (RNAP), an essential LTTR protein GcvA and its cognate promoter DNA. Structural analysis shows two N‐terminal DNA binding domains of GcvA (GcvA_DBD) dimerize and engage the GcvA activation binding sites, presenting the −35 element for specific recognition with the conserved σ70R4. In particular, the versatile C‐terminal domain of α subunit of RNAP directly interconnects with GcvA_DBD, σ70R4 and promoter DNA, providing more interfaces for stabilizing the complex. Moreover, molecular docking supports glycine as one potential inducer of GcvA, and single molecule photobleaching experiments kinetically visualize the occurrence of tetrameric GcvA‐engaged transcription activation complex as suggested for the other LTTR homologs. Thus, a general model for tetrameric LTTR‐dependent transcription activation is proposed. These findings will provide new structural and functional insights into transcription activation of the essential LTTRs.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0961-8368eISSN: 1469-896XDOI: 10.1002/pro.5012Titel-ID: cdi_proquest_miscellaneous_3053975165
- Format
- –
- Schlagworte
- Bacterial Proteins - chemistry, Bacterial Proteins - genetics, Bacterial Proteins - metabolism, Binding Sites, Cryoelectron Microscopy, C‐terminal domain of α subunit, Deoxyribonucleic acid, DNA, DNA-directed RNA polymerase, DNA-Directed RNA Polymerases - chemistry, DNA-Directed RNA Polymerases - genetics, DNA-Directed RNA Polymerases - metabolism, E coli, Escherichia coli - genetics, Escherichia coli - metabolism, Escherichia coli Proteins - chemistry, Escherichia coli Proteins - genetics, Escherichia coli Proteins - metabolism, GcvA_DBD, Gene Expression Regulation, Bacterial, Gene regulation, Genes, Glycine, LTTR‐dependent transcription activation complex, LysR‐type transcriptional regulators (LTTRs), Metabolic pathways, Models, Molecular, Molecular docking, Molecular Docking Simulation, Photobleaching, Prokaryotes, Promoter Regions, Genetic, Protein Multimerization, RNA polymerase, Structural analysis, Structure-function relationships, Transcription activation, Transcription Factors - chemistry, Transcription Factors - genetics, Transcription Factors - metabolism, Transcriptional Activation, Virulence