Transcriptional regulators CsoR (copper-sensitive operon repressor), RcnR, and FrmR, and related domains; this domain superfamily was previously known as DUF156
This superfamily includes various transcriptional regulators that respond to stressors including Cu(I), Ni(I), sulfite, and formaldehyde. It includes CsoR (copper-sensitive operon repressor) from Mycobacterium tuberculosis (MtCsoR), Bacillus subtilis (BsCsoR), Thermus thermophilus (TthCsoR), and Staphylococcus aureus (SaCsoR), Mycobacterium tuberculosis RicR (regulated in copper repressor, MtRicR), Escherichia coli RncR (formally known as YohL, nickel and cobalt-sensitive), Alcaligenes xylosoxidans NreA (nickel-sensitive), E. coli FrmR (formally known as YaiN, formaldehyde sensitive), and Staphylococcus aureus CstR (CsoR-like sulfur transferase repressor, NWMN_0026.5, SaCstR). CsoR is Cu(I)-inducible, and regulates the expression of genes involved in copper homeostasis. For example, TthCsoR binds the promoter region of the copZ-csoR-copA operon, and represses expression of these genes, which encode the copper chaperone CopZ, CsoR, and the copper efflux P-type ATPase CopA, respectively. In the presence of excess Cu(I), TthCsoR binds this ion, and is released from the DNA, allowing expression of the downstream genes. TthCsoR also senses other metal ions such as Cu(II), Zn(II), Ag(I), Cd(II) and Ni(II). CsoRs form a homotetramer (dimer of dimers). In the case of MtCsoR, two Cys residues on opposite subunits within each dimer, along with a His residue, bind the Cu(I) ion. These residues are conserved in the majority of members of this superfamily. Exceptions include the functionally uncharacterized Bacillus subtilis YrkD where there is an Asn instead of His (C-N-C), E.coli RcnR where there is a Thr instead of the second Cys (C-H-T), or TthCsoR and E.coli FrmR where there is a His instead of the second Cys and which have an additional N-terminal His (not found in those family members having C-H-C) that may also be involved in metal binding (H-C-H-H). A conserved Tyr and a Glu residue facilitate allosteric regulation of DNA binding. SaCstR regulates genes predicted to function in sulfur metabolism; it is thought that oxidation of the intersubunit Cys pair to a mixture of disulphide and trisulphide linkages by sulfite, results in a reduced affinity of SaCstR for the operator DNA. SaCstR exists as a mixture of oligomeric states, including dimers, tetramers and octamers. The sequence of SaCstR was not available at the time this hierarchy was curated and therefore was not included. Escherichia coli RncR represses expression of the gene encoding the nickel and cobalt-efflux protein RcnA. The gene encoding Alcaligenes xylosoxidans NreA is part of the nre nickel resistance locus located on the pTOM9 plasmid from thisbacteria. Escherichia coli FrmR regulates the formaldehyde degradation frmRAB operon.
Feature 1:putative metal binding site [ion binding site]
Evidence:
Comment:not all members of this superfamily are responsive to metal ions
Comment:based on binding of Mycobacterium tuberculosis CsoR to Cu(I)
Structure:2HH7; Mycobacterium tuberculosis CsoR binds Cu(I) in one of two copper binding sites; this is a partial binding site, the other Cys and His residue are contributed by the partner monomer of the homodimer
Comment:MtCsoR forms a homotetramer (dimer of dimers); each CsoR homodimer contains two symmetry-related subunit-bridging Cu(I) binding sites, one on either end. Each Cu(I) is coordinated by a Cys residue from one monomer, and a His and Cys residue from its partner monomer.
Jiyao W et al.(2023). "The conserved domain database in 2023.",