Crystal structure of the zinc-dependent MarR family transcriptional regulator AdcR in the Zn(II)-bound state

J Am Chem Soc. 2011 Dec 14;133(49):19614-7. doi: 10.1021/ja2080532. Epub 2011 Nov 21.

Abstract

Streptococcus pneumoniae adhesin competence regulator (AdcR), the first metal-dependent member of the multiple antibiotic resistance regulator (MarR) family of proteins, represses the transcription of a high-affinity zinc-specific uptake transporter, a group of surface antigen zinc-binding pneumococcal histidine triad proteins (PhtA, PhtB, PhtD, and PhtE), and an AdcA homologue (AdcAII). The 2.0 Å resolution structure of Zn(II)-bound AdcR reveals a highly helical two-fold-symmetric dimer with two distinct metal-binding sites per protomer. Zn(II) is tetrahedrally coordinated by E24, H42, H108, and H112 in what defines the primary sensing site in AdcR. Site 2 is a tetracoordinate site whose function is currently unknown. NMR methyl group perturbation experiments reveal that Zn(II) drives a global change in the structure of apo-AdcR that stabilizes a conformation that is compatible with DNA binding. This co-repression mechanism is unprecedented in MarR transcriptional regulators.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Bacterial Proteins / chemistry*
  • Bacterial Proteins / metabolism
  • Binding Sites
  • Crystallography, X-Ray
  • Models, Molecular
  • Protein Binding
  • Protein Multimerization
  • Protein Structure, Secondary
  • Streptococcus pneumoniae / chemistry*
  • Streptococcus pneumoniae / metabolism
  • Zinc / metabolism*

Substances

  • Bacterial Proteins
  • Zinc