Database accession: MF7000711
Name: Cadmium metal-sensor CMTR (Mycobacterium tuberculosis)
PDB ID: 2jsc
Experimental method: NMR
Assembly: Homodimer
Source organism: Mycobacterium tuberculosis
Primary publication of the structure:
Banci L, Bertini I, Cantini F, Ciofi-Baffoni S, Cavet JS, Dennison C, Graham AI, Harvie DR, Robinson NJ
NMR structural analysis of cadmium sensing by winged helix repressor CmtR.
(2007) J. Biol. Chem. 282: 30181-8
PMID: 17599915
Abstract:
CmtR from Mycobacterium tuberculosis is a winged helical DNA-binding repressor of the ArsR-SmtB metal-sensing family that senses cadmium and lead. Cadmium-CmtR is a dimer with the metal bound to Cys-102 from the C-terminal region of one subunit and two Cys associated with helix alphaR from the other subunit, forming a symmetrical pair of cadmium-binding sites. This is a significant novelty in the ArsR-SmtB family. The structure of the dimer could be solved at 312 K. The apoprotein at the same temperature is still a dimer, but it experiences a large conformational exchange at the dimer interface and within each monomer. This is monitored by an overall decrease of the number of nuclear Overhauser effects and by an increase of H(2)O-D(2)O exchange rates, especially at the dimeric interface, in the apo form with respect to the cadmium-bound state. The C-terminal tail region is completely unstructured in both apo and cadmium forms but becomes less mobile in the cadmium-bound protein due to the recruitment of Cys-102 as a metal-ligand. DNA binds to the apo dimer with a ratio 1:3 at millimolar concentration. Addition of cadmium to the apo-CmtR-DNA complex causes DNA detachment, restoring the NMR spectrum of free cadmium-CmtR. Cadmium binding across the dimer interface impairs DNA association by excluding the apo-conformers suited to bind DNA.
Annotations from the GeneOntology database. Only terms that fit at least two of the interacting proteins are shown. Molecular function:
cadmium ion binding cadmium ion binding
cadmium ion sensor activity cadmium ion sensor activity
DNA binding DNA binding
DNA-binding transcription factor activity DNA-binding transcription factor activity
lead ion binding lead ion binding
Biological process:
regulation of gene expression regulation of gene expression
response to cadmium ion response to cadmium ion
response to lead ion response to lead ion
Cellular component: not assigned
Structural annotations of the participating protein chains.Entry contents: 2 distinct polypeptide molecules
Chains: A, B
Notes: All chains according to the most probable oligomerization state stored in PDBe were considered.
Number of unique protein segments: 1
Name: HTH-type transcriptional regulator CmtR
Source organism: Mycobacterium tuberculosis
Length: 118 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMLTCEMRESALARLGRALADPTRCRILVALLDGVCYPGQLAAHLGLTRSNVSNHLSCLRGCGLVVATYEGRQVRYALADSHLARALGELVQVVLAVDTDQPCVAERAASGEAVEMTGS
UniProtKB AC: P9WMI9 (positions: 11-106)
Coverage: 81%
Name: HTH-type transcriptional regulator CmtR
Source organism: Mycobacterium tuberculosis
Length: 118 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMLTCEMRESALARLGRALADPTRCRILVALLDGVCYPGQLAAHLGLTRSNVSNHLSCLRGCGLVVATYEGRQVRYALADSHLARALGELVQVVLAVDTDQPCVAERAASGEAVEMTGS
UniProtKB AC: P9WMI9 (positions: 10-106)
Coverage: 82%
Evidence demonstrating that the participating proteins are unstructured prior to the interaction and their folding is coupled to binding. Representative domain in related structures: Winged helix DNA-binding domain (ArsR family) transcriptional regulator
Evidence level: Indirect evidence
Evidence coverage: Only some parts of the structure participates in mutual synergistic folding.
Complex Evidence:
The N-terminal portion of the ArsR family transcriptional regulator, Mj223, is a helix-turn-helix (HTH) winged-helix DNA-binding motif. The C-terminal region of the protein is composed of two leucine-rich α-helices (H5 and H6) that form an antiparallel four-helix bundle with a large, hydrophobic interaction surface on dimerization that forms the hydrophobic core of the dimer (PMID:12471609, PMID:9466913). The C-terminal dimerization subdomain is a nice case of MSF. The protein is a dimer in solution (Dynamic light scattering) (PMID:12471609).
Chain A:
N/A
Chain B:
N/A
Surface and contacts features:
Structures from the PDB that contain the same number of proteins, and the proteins from the two structures show a sufficient degree of pairwise similarity, i.e. they belong to the same UniRef90 cluster (the full proteins exhibit at least 90% sequence identity) and convey roughly the same region to their respective interactions (the two regions from the two proteins share a minimum of 70% overlap). Download the CIF file (.cif)
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