Motion of the DNA-binding domain with respect to the core of the diphtheria toxin repressor (DtxR) revealed in the crystal structures of apo- and holo-DtxR

J Biol Chem. 1998 Aug 28;273(35):22420-7. doi: 10.1074/jbc.273.35.22420.

Abstract

The diphtheria toxin repressor (DtxR) from Corynebacterium diphtheriae is a divalent metal-activated repressor of chromosomal genes that encode proteins responsible for siderophore-mediated iron uptake and also of the gene of certain corynebacteriophages that encodes diphtheria toxin. DtxR consists of two 25.3-kDa three-domain subunits and is a member of a family of related repressor proteins in several Gram-positive bacterial species, some of which are important human pathogens. In this paper, we report on the first high resolution crystal structures of apo-DtxR in two related space groups. In addition, crystal structures of Zn-DtxR were determined in the same two space groups. The resolutions of the structures range from 2.2 to 2.4 A. The four refined models of the apo- and the holo-repressor exhibit quite similar metal binding centers, which do, however, show higher thermal motion in the apo-structures. All four structures reported differ from each other in one important aspect. The N-terminal DNA-binding domain and the last 20 residues of the dimerization domain of each subunit move significantly with respect to the core of the DtxR dimer, which consists of residues 74-120 from both subunits. These results provide the first indication of a conformational change that may occur upon binding of the holo-repressor to DNA.

Publication types

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

MeSH terms

  • Bacterial Proteins / chemistry
  • Bacterial Proteins / metabolism*
  • Binding Sites
  • Corynebacterium diphtheriae / metabolism
  • Crystallography, X-Ray
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / metabolism*
  • Metals / metabolism
  • Models, Molecular
  • Protein Conformation
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism

Substances

  • Bacterial Proteins
  • DNA-Binding Proteins
  • DtxR protein, Corynebacterium diphtheriae
  • Metals
  • Recombinant Proteins

Associated data

  • PDB/1BI0
  • PDB/1BI1
  • PDB/1BI2
  • PDB/1BI3