The SorC family of transcriptional regulators plays a crucial role in controlling the carbohydrate metabolism and quorum sensing. We employed an integrative approach combining X-ray crystallography and cryo-electron microscopy to investigate architecture and functional mechanism of two prototypical representatives of two sub-classes of the SorC family: DeoR and CggR from Bacillus subtilis. Despite possessing distinct DNA-binding domains, both proteins form similar tetrameric assemblies when bound to their respective DNA operators. Structural analysis elucidates the process by which the CggR-regulated gapA operon is derepressed through the action of two effectors: fructose-1,6-bisphosphate and newly confirmed dihydroxyacetone phosphate. Our findings provide the first comprehensive understanding of the DNA binding mechanism of the SorC-family proteins, shedding new light on their functional characteristics.

CryoElectron Microscopy and Tomography Core Facility Central European Institute of Technology Brno 601 77 Czechia

Laboratory of Microbial Genetics and Gene Expression Institute of Microbiology of the Czech Academy of Sciences Vídeňská 1083 Prague 142 20 Czechia

Research Institute of Molecular Pathology Campus ViennaBiocenter 1 1030 Vienna Austria

Structural Biology Institute of Organic Chemistry and Biochemistry of Czech Academy of Sciences Prague 166 10 Czechia

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Nucleic Acids Res. 2025 Feb 27;53(5):gkaf195. doi: 10.1093/nar/gkaf195. PubMed

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Structure and function of bacterial transcription regulators of the SorC family