Biophysical and structural characterization of a zinc-responsive repressor of the MarR superfamily

PLoS One. 2019 Feb 12;14(2):e0210123. doi: 10.1371/journal.pone.0210123. eCollection 2019.

Abstract

The uptake of zinc, which is vital in trace amounts, is tightly controlled in bacteria. For this control, bacteria of the Streptococcaceae group use a Zn(II)-binding repressor named ZitR in lactococci and AdcR in streptococci, while other bacteria use a Zur protein of the Ferric uptake regulator (Fur) superfamily. ZitR and AdcR proteins, characterized by a winged helix-turn-helix DNA-binding domain, belong to the multiple antibiotic resistance (MarR) superfamily, where they form a specific group of metallo-regulators. Here, one such Zn(II)-responsive repressor, ZitR of Lactococcus lactis subspecies cremoris strain MG1363, is characterized. Size Exclusion Chromatography-coupled to Multi Angle Light Scattering, Circular Dichroism and Isothermal Titration Calorimetry show that purified ZitR is a stable dimer complexed to Zn(II), which is able to bind its two palindromic operator sites on DNA fragments. The crystal structure of ZitR holo-form (Zn(II)4-ZitR2), has been determined at 2.8 Å resolution. ZitR is the fourth member of the MarR metallo-regulator subgroup whose structure has been determined. The folding of ZitR/AdcR metallo-proteins is highly conserved between both subspecies (cremoris or lactis) in the Lactococcus lactis species and between species (Lactococcus lactis and Streptococcus pneumoniae or pyogenes) in the Streptococcaceae group. It is also similar to the folding of other MarR members, especially in the DNA-binding domain. Our study contributes to better understand the biochemical and structural properties of metallo-regulators in the MarR superfamily.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Bacterial Proteins / chemistry
  • Bacterial Proteins / metabolism*
  • Binding Sites
  • Crystallography, X-Ray
  • Lactococcus lactis / chemistry
  • Lactococcus lactis / metabolism*
  • Models, Molecular
  • Protein Binding
  • Protein Conformation
  • Protein Multimerization
  • Repressor Proteins / chemistry
  • Repressor Proteins / metabolism*
  • Zinc / metabolism*

Substances

  • Bacterial Proteins
  • Repressor Proteins
  • Zinc

Grants and funding

This work was supported by the French Infrastructure for Integrated Structural Biology (FRISBI), ANR-10-INSB-05-01.