2KJB

Solution structure of CzrA in the DNA bound state

Summary for 2KJB

• Entry DOI: 10.2210/pdb2kjb/pdb
• Related: 2KJC
• Descriptor: CzrA protein (1 entity in total)
• Functional Keywords: czra, dna-binding, transcription, transcription regulation, transcription regulator
• Biological source: Staphylococcus aureus
• Total number of polymer chains: 2
• Total formula weight: 23983.42

Authors

Arunkumar, A.I.,Campanello, G.C.,Giedroc, D.P. (deposition date: 2009-05-27, release date: 2009-11-10, Last modification date: 2024-05-22)

Primary citation

Arunkumar, A.I.,Campanello, G.C.,Giedroc, D.P.
Solution structure of a paradigm ArsR family zinc sensor in the DNA-bound state
Proc.Natl.Acad.Sci.USA, 106:18177-18182, 2009

PubMed 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.

PubMed: 19822742
DOI: 10.1073/pnas.0905558106

Experimental method

SOLUTION NMR