Database accession: MF7000713
Name: NmtR (apo form)
PDB ID: 2lkp
Experimental method: NMR
Assembly: Homodimer
Source organism: Mycobacterium tuberculosis
Primary publication of the structure:
Lee CW, Chakravorty DK, Chang FM, Reyes-Caballero H, Ye Y, Merz KM, Giedroc DP
Solution structure of Mycobacterium tuberculosis NmtR in the apo state: insights into Ni(II)-mediated allostery.
(2012) Biochemistry 51: 2619-29
PMID: 22394357
Abstract:
Mycobacterium tuberculosis is an obligate human respiratory pathogen that encodes approximately 10 arsenic repressor (ArsR) family regulatory proteins that allow the organism to respond to a wide range of changes in its immediate microenvironment. How individual ArsR repressors have evolved to respond to selective stimuli is of intrinsic interest. The Ni(II)/Co(II)-specific repressor NmtR and related actinomycete nickel sensors harbor a conserved N-terminal α-NH(2)-Gly2-His3-Gly4 sequence. Here, we present the solution structure of homodimeric apo-NmtR and show that the core of the molecule adopts a typical winged-helix ArsR repressor (α1-α2-α3-αR-β1-β2-α5) "open conformation" that is similar to that of the related zinc sensor Staphylococcus aureus CzrA, but harboring long, flexible N-terminal (residues 2-16) and C-terminal (residues 109-120) extensions. Binding of Ni(II) to the regulatory sites induces strong paramagnetic broadening of the α5 helical region and the extreme N-terminal tail to residue 10. Ratiometric pulse chase amidination mass spectrometry reveals that the rate of amidination of the α-amino group of Gly2 is strongly attenuated in the Ni(II) complex relative to the apo state and noncognate Zn(II) complex. Ni(II) binding also induces dynamic disorder on the microsecond to millisecond time scale of key DNA interacting regions that likely contributes to the negative regulation of DNA binding by Ni(II). Molecular dynamics simulations and quantum chemical calculations reveal that NmtR readily accommodates a distal Ni(II) hexacoordination model involving the α-amine and His3 of the N-terminal region and α5 residues Asp91', His93', His104, and His107, which collectively define a new metal sensing site configuration in ArsR family regulators.
Annotations from the GeneOntology database. Only terms that fit at least two of the interacting proteins are shown. Molecular function:
DNA-binding transcription factor activity DNA-binding transcription factor activity
Biological process: not assigned
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: Transcriptional regulator, ArsR family
Source organism: Mycobacterium tuberculosis
Length: 135 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMIICSFISLGIGCLTMGHGVEGRNRPSAPLDSQAAAQVASTLQALATPSRLMILTQLRNGPLPVTDLAEAIGMEQSAVSHQLRVLRNLGLVVGDRAGRSIVYSLYDTHVAQLLDEAIYHSEHLHLGLSDRHPSAG
UniProtKB AC: Q7D4Y3 (positions: 17-135)
Coverage: 88%
Name: Transcriptional regulator, ArsR family
Source organism: Mycobacterium tuberculosis
Length: 135 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMIICSFISLGIGCLTMGHGVEGRNRPSAPLDSQAAAQVASTLQALATPSRLMILTQLRNGPLPVTDLAEAIGMEQSAVSHQLRVLRNLGLVVGDRAGRSIVYSLYDTHVAQLLDEAIYHSEHLHLGLSDRHPSAG
UniProtKB AC: Q7D4Y3 (positions: 17-135)
Coverage: 88%
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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