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.
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.
Pohl
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Department of Biological Structure, University of Washington, Seattle, Washington 98195-7742, USA.
Holmes
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RK
Hol
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WG
D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism*; D001665:Binding Sites; D003353:Corynebacterium diphtheriae / Q000378:metabolism; D018360:Crystallography, X-Ray; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D008670:Metals / Q000378:metabolism; D008958:Models, Molecular; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism
D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; C075586:DtxR protein, Corynebacterium diphtheriae; D008670:Metals; D011994:Recombinant Proteins