Database accession: MF7000756
Name: PcaV transcriptional regulator (Streptomyces coelicolor)
PDB ID: 4g9y
Experimental method: X-ray (2.05 Å)
Assembly: Homodimer
Source organism: Streptomyces coelicolor
Primary publication of the structure:
Davis JR, Brown BL, Page R, Sello JK
Study of PcaV from Streptomyces coelicolor yields new insights into ligand-responsive MarR family transcription factors.
(2013) Nucleic Acids Res. 41: 3888-900
PMID: 23396446
Abstract:
MarR family proteins constitute a group of >12 000 transcriptional regulators encoded in bacterial and archaeal genomes that control gene expression in metabolism, stress responses, virulence and multi-drug resistance. There is much interest in defining the molecular mechanism by which ligand binding attenuates the DNA-binding activities of these proteins. Here, we describe how PcaV, a MarR family regulator in Streptomyces coelicolor, controls transcription of genes encoding β-ketoadipate pathway enzymes through its interaction with the pathway substrate, protocatechuate. This transcriptional repressor is the only MarR protein known to regulate this essential pathway for aromatic catabolism. In in vitro assays, protocatechuate and other phenolic compounds disrupt the PcaV-DNA complex. We show that PcaV binds protocatechuate in a 1:1 stoichiometry with the highest affinity of any MarR family member. Moreover, we report structures of PcaV in its apo form and in complex with protocatechuate. We identify an arginine residue that is critical for ligand coordination and demonstrate that it is also required for binding DNA. We propose that interaction of ligand with this arginine residue dictates conformational changes that modulate DNA binding. Our results provide new insights into the molecular mechanism by which ligands attenuate DNA binding in this large family of transcription factors.
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:
regulation of DNA-templated transcription regulation of DNA-templated transcription
response to stress response to stress
Cellular component: not assigned
Structural annotations of the participating protein chains.Entry contents: 2 distinct polypeptide molecules
Chains: A, A-2
Notes: All chains according to the most probable oligomerization state stored in PDBe were considered.
Number of unique protein segments: 1
Name: Transcriptional regulator
Source organism: Streptomyces coelicolor
Length: 154 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMAAVDLATHPGHLARRLQQAHYLLWNTMVSEETTSPQYAVLNALVAEPGLDQRTVGERVGLDRSTIAEVVSRLGRRGLLDKVRDPQDGRRSLLRLTDEGLRVHRRLGVRIARMNQVFLAPLAADEQAVFFDLIRRVADAAEGLRNPAEPAVAPG
UniProtKB AC: Q9XAM6 (positions: 8-143)
Coverage: 88%
Name: Transcriptional regulator
Source organism: Streptomyces coelicolor
Length: 154 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMAAVDLATHPGHLARRLQQAHYLLWNTMVSEETTSPQYAVLNALVAEPGLDQRTVGERVGLDRSTIAEVVSRLGRRGLLDKVRDPQDGRRSLLRLTDEGLRVHRRLGVRIARMNQVFLAPLAADEQAVFFDLIRRVADAAEGLRNPAEPAVAPG
UniProtKB AC: Q9XAM6 (positions: 8-143)
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 (MarR type II) transcriptional regulator
Evidence level: Indirect evidence
Evidence coverage: Only some parts of the structure participates in mutual synergistic folding.
Complex Evidence:
Thermal unfolding measured with circular dichroism of the MarR family protein, HucR, suggested two-state model of unfolding (PMID:15448166). Also, a decrease in pH induced a molten globule-like state, where the protein remained in dimeric form (PMID:27282811). Helices 1, 2, 6 and 7 form the dimerization subdomain, they form an apparently stable dimer interface that preconfigures the DNA recognition HTH subdomain for DNA binding (PMID:16750221).
Chain A:
N/A
Chain A-2:
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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