1R1V

Crystal structure of the metal-sensing transcriptional repressor CzrA from Staphylococcus aureus in the Zn2-form

Summary for 1R1V

• Entry DOI: 10.2210/pdb1r1v/pdb
• Related: 1R1T 1R1U 1R22 1R23 1SMT
• Descriptor: repressor protein, ZINC ION (3 entities in total)
• Functional Keywords: dna binding, transcriptional regulation, winged hth protein, transcription repressor
• Biological source: Staphylococcus aureus
• Total number of polymer chains: 2
• Total formula weight: 24277.05

Authors

Eicken, C.,Pennella, M.A.,Chen, X.,Koshlap, K.M.,VanZile, M.L.,Sacchettini, J.C.,Giedroc, D.P. (deposition date: 2003-09-25, release date: 2004-05-18, Last modification date: 2023-08-23)

Primary citation

Eicken, C.,Pennella, M.A.,Chen, X.,Koshlap, K.M.,VanZile, M.L.,Sacchettini, J.C.,Giedroc, D.P.
A metal-ligand-mediated intersubunit allosteric switch in related SmtB/ArsR zinc sensor proteins.
J.Mol.Biol., 333:683-695, 2003

PubMed Abstract: The origin of metal ion selectivity by members of the SmtB/ArsR family of bacterial metal-sensing transcriptional repressors and the mechanism of negative allosteric regulation of DNA binding is poorly understood. Here, we report that two homologous zinc sensors, Staphylococcus aureus CzrA and cyanobacterial SmtB, are "winged" helix homodimeric DNA-binding proteins that bind Zn(II) to a pair of tetrahedral, interhelical binding sites, with two ligands derived from the alpha5 helix of one subunit, Asp84 O(delta1) (Asp104 in SmtB), His86 N(delta1) (His106), and two derived from the alpha5 helix of the other, His97' N(delta1) (His117') and His100' N(epsilon2) (Glu120'). Formation of the metal chelate drives a quaternary structural switch mediated by an intersubunit hydrogen-binding network that originates with the non-liganding N(epsilon2) face of His97 in CzrA (His117 in SmtB) that stabilizes a low-affinity, DNA-binding conformation. The structure of the Zn(1) SmtB homodimer shows that both metal-binding sites of the dimer must be occupied for the quaternary structural switch to occur. Thus, a critical zinc-ligating histidine residue obligatorily couples formation of the metal-sensing coordination chelate to changes in the conformation and dynamics of the putative DNA-binding helices.

PubMed: 14568530
DOI: 10.1016/j.jmb.2003.09.007

Experimental method

X-RAY DIFFRACTION (2.3 Å)