Database accession: MF7000712
Name: CzrA with Zn
PDB ID: 2kjc
Experimental method: NMR
Assembly: Homodimer
Source organism: Staphylococcus aureus
Primary publication of the structure:
Arunkumar AI, Campanello GC, Giedroc DP
Solution structure of a paradigm ArsR family zinc sensor in the DNA-bound state.
(2009) Proc. Natl. Acad. Sci. U.S.A. 106: 18177-82
PMID: 19822742
Abstract:
Staphylococcus aureus CzrA is a zinc-dependent transcriptional repressor from the ubiquitous ArsR family of metal sensor proteins. Zn(II) binds to a pair of intersubunit C-terminal alpha5-sensing sites, some 15 A distant from the DNA-binding interface, and allosterically inhibits DNA binding. This regulation is characterized by a large allosteric coupling free energy (DeltaGc) of approximately +6 kcal mol(-1), the molecular origin of which is poorly understood. Here, we report the solution quaternary structure of homodimeric CzrA bound to a palindromic 28-bp czr operator, a structure that provides an opportunity to compare the two allosteric "end" states of an ArsR family sensor. Zn(II) binding drives a quaternary structural switch from a "closed" DNA-binding state to a low affinity "open" conformation as a result of a dramatic change in the relative orientations of the winged helical DNA binding domains within the dimer. Zn(II) binding also effectively quenches both rapid and intermediate timescale internal motions of apo-CzrA while stabilizing the native state ensemble. In contrast, DNA binding significantly enhances protein motions in the allosteric sites and reduces the stability of the alpha5 helices as measured by H-D solvent exchange. This study reveals how changes in the global structure and dynamics drive a long-range allosteric response in a large subfamily of bacterial metal sensor proteins, and provides insights on how other structural classes of ArsR sensor proteins may be regulated by metal binding.
Annotations from the GeneOntology database. Only terms that fit at least two of the interacting proteins are shown. Molecular function:
DNA binding DNA binding
DNA-binding transcription factor activity DNA-binding transcription factor activity
identical protein binding identical protein 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
Source organism: Staphylococcus aureus
Length: 106 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMSEQYSEINTDTLERVTEIFKALGDYNRIRIMELLSVSEASVGHISHQLNLSQSNVSHQLKLLKSVHLVKAKRQGQSMIYSLDDIHVATMLKQAIHHANHPKESGL
UniProtKB AC: O85142 (positions: 9-103)
Coverage: 89%
Name: Transcriptional regulator
Source organism: Staphylococcus aureus
Length: 106 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMSEQYSEINTDTLERVTEIFKALGDYNRIRIMELLSVSEASVGHISHQLNLSQSNVSHQLKLLKSVHLVKAKRQGQSMIYSLDDIHVATMLKQAIHHANHPKESGL
UniProtKB AC: O85142 (positions: 9-103)
Coverage: 89%
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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