Database accession: MF7000318
Name: PadR-family transcriptional regulator Rv3488 (Mycobacterium tuberculosis)
PDB ID: 5zi8
Experimental method: X-ray (2.20 Å)
Assembly: Homodimer
Source organism: Mycobacterium tuberculosis
Primary publication of the structure:
Kumari M, Pal RK, Mishra AK, Tripathi S, Biswal BK, Srivastava KK, Arora A
Structural and functional characterization of the transcriptional regulator Rv3488 of H37Rv.
(2018) Biochem. J. 475: 3393-3416
PMID: 30266832
Abstract:
Rv3488 of Mycobacterium tuberculosis H37Rv has been assigned to the phenolic acid decarboxylase repressor (PadR) family of transcriptional regulators that play key roles in multidrug resistance and virulence of prokaryotes. The binding of cadmium, zinc, and several other metals to Rv3488 was discovered and characterized by isothermal titration calorimetery to be an exothermic process. Crystal structures of apo-Rv3488 and Rv3488 in complex with cadmium or zinc ions were determined by X-ray crystallography. The structure of Rv3488 revealed a dimeric protein with N-terminal winged-helix-turn-helix DNA-binding domains composed of helices α1, α2, α3, and strands β1 and β2, with the dimerization interface being formed of helices α4 and α1. The overall fold of Rv3488 was similar to PadR-s2 and metal sensor transcriptional regulators. In the crystal structure of Rv3488-Cd complex, two octahedrally coordinated Cd2+ ions were present, one for each subunit. The same sites were occupied by zinc ions in the structure of Rv3488-Zn, with two additional zinc ions complexed in one monomer. EMSA studies showed specific binding of Rv3488 with its own 30-bp promoter DNA. The functional role of Rv3488 was characterized by expressing the rv3488 gene under the control of hsp60 promoter in Mycobacterium smegmatis Expression of Rv3488 increased the intracellular survival of recombinant M. smegmatis in murine macrophage cell line J774A.1 and also augmented its tolerance to Cd2+ ions. Overall, the studies show that Rv3488 may have transcription regulation and metal-detoxifying functions and its expression in M. smegmatis increases intracellular survival, perhaps by counteracting toxic metal stress.
Annotations from the GeneOntology database. Only terms that fit at least two of the interacting proteins are shown. Molecular function:
DNA binding DNA binding
metal ion binding metal ion binding
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 Rv3488
Source organism: Mycobacterium tuberculosis
Length: 107 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMREFQRAAVRLHILHHAADNEVHGAWLTQELSRHGYRVSPGTLYPTLHRLEADGLLVSEQRVVDGRARRVYRATPAGRAALTEDRRALEELAREVLGGQSHTAGNGT
UniProtKB AC: I6X7F9 (positions: 1-101)
Coverage: 94%
Name: Transcriptional regulator Rv3488
Source organism: Mycobacterium tuberculosis
Length: 107 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMREFQRAAVRLHILHHAADNEVHGAWLTQELSRHGYRVSPGTLYPTLHRLEADGLLVSEQRVVDGRARRVYRATPAGRAALTEDRRALEELAREVLGGQSHTAGNGT
UniProtKB AC: I6X7F9 (positions: 1-99)
Coverage: 92%
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 (PadR family) transcriptional regulator
Evidence level: Direct evidence
Evidence coverage: Only some parts of the structure participates in mutual synergistic folding.
Complex Evidence:
AphA monomers were found to be highly unstable (PMID:15647287). AphA is a dimer with an N-terminal winged helix DNA-binding domain and a unique C-terminal antiparallel coiled coil domain that serves as its primary dimerization interface and is a case of mutual synergistic folding (MSF). Another PadR family transcriptional regulator, Rv3488, was shown to be a dimer in solution (PMID:30266832), while differential scanning calorimetry-based thermal denaturation data suggested that the PadR family Rv1176c follows two-state unfolding (PMID:38417748).
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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