PDBsum entry 2kjb

Go to PDB code: 
protein Protein-protein interface(s) links
Transcription regulator PDB id
Protein chains
95 a.a. *
* Residue conservation analysis
PDB id:
Name: Transcription regulator
Title: Solution structure of czra in the DNA bound state
Structure: Czra protein. Chain: a, b. Synonym: repressor protein. Engineered: yes
Source: Staphylococcus aureus. Organism_taxid: 1280. Gene: rzca, czra. Expressed in: escherichia coli. Expression_system_taxid: 562.
NMR struc: 21 models
Authors: A.I.Arunkumar,G.C.Campanello,D.P.Giedroc
Key ref:
A.I.Arunkumar et al. (2009). Solution structure of a paradigm ArsR family zinc sensor in the DNA-bound state. Proc Natl Acad Sci U S A, 106, 18177-18182. PubMed id: 19822742 DOI: 10.1073/pnas.0905558106
27-May-09     Release date:   10-Nov-09    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
O85142  (O85142_STAAU) -  ArsR family transcriptional regulator
106 a.a.
95 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     transcription, DNA-dependent   2 terms 
  Biochemical function     DNA binding     3 terms  


DOI no: 10.1073/pnas.0905558106 Proc Natl Acad Sci U S A 106:18177-18182 (2009)
PubMed id: 19822742  
Solution structure of a paradigm ArsR family zinc sensor in the DNA-bound state.
A.I.Arunkumar, G.C.Campanello, D.P.Giedroc.
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.
  Selected figure(s)  
Figure 1.
Solution structure of CzrO DNA-bound CzrA. (A) Backbone heavy atom (N, Cα, and C') overlay of 20 lowest-energy structures of DNA bound CzrA (see Table S2 for structure statistics; unstructured residues 100–103 of the bundle are not shown in this view for clarity). The ribbon diagram in the overlay represents the mean structure of the ensemble and the two subunits are shaded salmon and red. (B) Ribbon diagram representation of the global overlay of DNA bound CzrA and the crystal structure of Zn(II) CzrA (8). The subunits of DNA bound CzrA are colored as in A and the two subunits of Zn(II) CzrA are colored slate and blue. Zn(II) ions are colored yellow. (C) Another view of the same overlay as in B (rotated 45°) and the green arrows represent the direction of the quaternary structural change.
Figure 2.
Distinct conformational states of α5 metal sensor proteins. (A) Overlay of the apo SmtB (magenta ribbon), Zn(II)-bound CzrA (light blue ribbon) and DNA-bound CzrA (salmon ribbon). The “right” subunit is overlaid to better show the quaternary structural differences. (B) Effect of binding DNA on apo CzrA structure is mapped using a ^1H HN chemical shift perturbation experiment. Colors on the ribbon are ramped according to Δδ ppm as follows: gray, Δδ<0.2 ppm; magenta, 0.2<Δδ<0.8 and red; 0.8<Δδ<1.5 ppm. (C) A comparison of the short time scale ^15N relaxation dynamics of Zn[2] CzrA vs. apo-CzrA (see Fig. S2 for primary data). Blue, increased S^2 by ≥ 0.02 on Zn(II) binding; yellow, decreased S^2 by ≤ –0.02 on Zn(II) binding; purple, residues in apo-CzrA that exhibit measurable R[ex] ≥ 1 s^−1 that is completely dampened upon Zn(II) binding; orange, the single residue in Zn[2] CzrA for which there is measurable R[ex] ≥ 1 s^−1 (L35).
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20442958 D.Osman, and J.S.Cavet (2010).
Bacterial metal-sensing proteins exemplified by ArsR-SmtB family repressors.
  Nat Prod Rep, 27, 668-680.  
20534443 L.Ni, W.Xu, M.Kumaraswami, and M.A.Schumacher (2010).
From the Cover: Plasmid protein TubR uses a distinct mode of HTH-DNA binding and recruits the prokaryotic tubulin homolog TubZ to effect DNA partition.
  Proc Natl Acad Sci U S A, 107, 11763-11768.
PDB codes: 3m89 3m8e 3m8f 3m8k 3m9a
19995076 N.E.Grossoehme, and D.P.Giedroc (2009).
Energetics of allosteric negative coupling in the zinc sensor S. aureus CzrA.
  J Am Chem Soc, 131, 17860-17870.  
19928961 Z.Ma, D.M.Cowart, B.P.Ward, R.J.Arnold, R.D.DiMarchi, L.Zhang, G.N.George, R.A.Scott, and D.P.Giedroc (2009).
Unnatural amino acid substitution as a probe of the allosteric coupling pathway in a mycobacterial Cu(I) sensor.
  J Am Chem Soc, 131, 18044-18045.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.