Structural characterization of the active form of PerR: insights into the metal-induced activation of PerR and Fur proteins for DNA binding.
In Bacillus subtilis, the transcription factor PerR is an iron dependant sensor of H(2)O(2). The sensing mechanism relies on a selective metal catalysed oxidation of two histidine residues of the regulatory site. Here we present the first crystal structure of the active PerR protein in complex with a Mn(2+) ion. In addition, X-ray absorption spectroscopy experiments were performed to characterize the corresponding iron form of the protein. Both studies reveal a penta-coordinate arrangement of the regulatory site that involves three histidines and two aspartates. One of the histidine ligand belongs to the N-terminal domain. Binding of this residue to the regulatory metal allows the protein to adopt a caliper-like conformation suited to DNA binding. Since this histidine is conserved in all PerR and a vast majority of Fur proteins, it is likely that the allosteric switch induced by the regulatory metal is general for this family of metalloregulators.
Jacquamet
L
L
Institut de Biologie Structurale CEA-CNRS-UJF, LCCP, GSY, 41 rue Jules Horowitz, 38027 Grenoble Cedex 1, France.
Traoré
D A K
DA
Ferrer
J-L
JL
Proux
O
O
Testemale
D
D
Hazemann
J-L
JL
Nazarenko
E
E
El Ghazouani
A
A
Caux-Thang
C
C
Duarte
V
V
Latour
J-M
JM
D001412:Bacillus subtilis / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites; D015964:Gene Expression Regulation, Bacterial; D006861:Hydrogen Peroxide / Q000378:metabolism*; D008274:Magnesium / Q000378:metabolism; D008958:Models, Molecular; D020836:Protein Structure, Quaternary; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D013057:Spectrum Analysis; D014965:X-Rays
D001426:Bacterial Proteins; D012097:Repressor Proteins; C122138:peroxide repressor proteins; D006861:Hydrogen Peroxide; D008274:Magnesium