Database accession: MF7000758
Name: HucR mutant (HucR-E48Q) (Deinococcus radiodurans)
PDB ID: 5dd8
Experimental method: X-ray (2.05 Å)
Assembly: Homodimer
Source organism: Deinococcus radiodurans
Primary publication of the structure:
Deochand DK, Perera IC, Crochet RB, Gilbert NC, Newcomer ME, Grove A
Histidine switch controlling pH-dependent protein folding and DNA binding in a transcription factor at the core of synthetic network devices.
(2016) Mol Biosyst 12: 2417-26
PMID: 27282811
Abstract:
Therapeutic strategies have been reported that depend on synthetic network devices in which a urate-sensing transcriptional regulator detects pathological levels of urate and triggers production or release of urate oxidase. The transcription factor involved, HucR, is a member of the multiple antibiotic resistance (MarR) protein family. We show that protonation of stacked histidine residues at the pivot point of long helices that form the scaffold of the dimer interface leads to reversible formation of a molten globule state and significantly attenuated DNA binding at physiological temperatures. We also show that binding of urate to symmetrical sites in each protein lobe is communicated via the dimer interface. This is the first demonstration of regulation of a MarR family transcription factor by pH-dependent interconversion between a molten globule and a compact folded state. Our data further suggest that HucR may be utilized in synthetic devices that depend on detection of pH changes.
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, 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, MarR family
Source organism: Deinococcus radiodurans
Length: 181 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMSARMDNDTAALLERIRSDWARLNHGQGPDSDGLTPSAGPMLTLLLLERLHAALGREIERTYAASGLNAAGWDLLLTLYRSAPPEGLRPTELSALAAISGPSTSNRIVRLLEKGLIERREDERDRRSASIRLTPQGRALVTHLLPAHLATTQRVLAPLSAQEQRTLEELAGRMLAGLEQGV
UniProtKB AC: Q9RV71 (positions: 8-179)
Coverage: 95%
Name: Transcriptional regulator, MarR family
Source organism: Deinococcus radiodurans
Length: 181 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMSARMDNDTAALLERIRSDWARLNHGQGPDSDGLTPSAGPMLTLLLLERLHAALGREIERTYAASGLNAAGWDLLLTLYRSAPPEGLRPTELSALAAISGPSTSNRIVRLLEKGLIERREDERDRRSASIRLTPQGRALVTHLLPAHLATTQRVLAPLSAQEQRTLEELAGRMLAGLEQGV
UniProtKB AC: Q9RV71 (positions: 8-179)
Coverage: 95%
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 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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