biostudies-literatureSoltysova MMinistry of EducationEuropean Union - Next Generation EUEuropean UnionNational Institute of virology and bacteriologyCzech Science FoundationInstitute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences7305-7320https://www.ebi.ac.uk/biostudies/studies/S-EPMC11229326biostudies-literatureUnknown52(12)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 understanNucleic acids researchStructural characterization of two prototypical repressors of SorC family reveals tetrameric assemblies on DNA and mechanism of function.PMC11229326LX22NPO510323-06295SNovacek JRezacova PGrishkovskaya ISkubnik KSieglova IBabiak MSkerlova JPachl PKrasny LSoltysova MFarolfi MFabry MfalseStructural characterization of two prototypical repressors of SorC family reveals tetrameric assemblies on DNA and mechanism of function.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 understan2024-01-01T00:00:00Z2024 Jul2026-04-07T16:17:14.463Z2025-04-04T11:24:24.351ZS-EPMC112293263884293610.1093/nar/gkae434