Crystal structure of the IrrE protein, a central regulator of DNA damage repair in deinococcaceae.
Deinococcaceae are famous for their extreme radioresistance. Transcriptome analysis in Deinococcus radiodurans revealed a group of genes up-regulated in response to desiccation and ionizing radiation. IrrE, a novel protein initially found in D. radiodurans, was shown to be a positive regulator of some of these genes. Deinococcus deserti irrE is able to restore radioresistance in a D. radiodurans DeltairrE mutant. The D. deserti IrrE crystal structure reveals a unique combination of three domains: one zinc peptidase-like domain, one helix-turn-helix motif and one GAF-like domain. Mutant analysis indicates that the first and third domains are critical regions for radiotolerance. In particular, mutants affected in the putative zinc-binding site are as sensitive to gamma and UV irradiation as the DeltairrE bacteria, and radioresistance is strongly decreased with the H217L mutation present in the C-terminal domain. In addition, modeling of IrrE-DNA interaction suggests that the observed IrrE structure may not bind double-stranded DNA through its central helix-turn-helix motif and that IrrE is not a classic transcriptional factor that activates gene expression by its direct binding to DNA. We propose that the putative protease activity of IrrE could be a key element of transcription enhancement and that a more classic transcription factor, possibly an IrrE substrate, would link IrrE to transcription of genes specifically involved in radioresistance.
Vujicić-Zagar
Andreja
A
Laboratoire des Protéines Membranaires, Institut de Biologie Structurale UMR5075 (CEA/CNRS/Université Joseph Fourier), 41 rue Jules Horowitz, 38027 Grenoble Cedex 01, France.
Dulermo
Remi
R
Le Gorrec
Madalen
M
Vannier
Françoise
F
Servant
Pascale
P
Sommer
Suzanne
S
de Groot
Arjan
A
Serre
Laurence
L
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics; D018360:Crystallography, X-Ray; D004252:DNA Mutational Analysis; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D034301:Deinococcus / Q000737:chemistry* / Q000201:enzymology / Q000528:radiation effects; D005720:Gamma Rays; D050296:Microbial Viability; D008958:Models, Molecular; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010447:Peptide Hydrolases / Q000235:genetics; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000737:chemistry* / Q000235:genetics; D014466:Ultraviolet Rays
D001426:Bacterial Proteins; D004269:DNA, Bacterial; D014157:Transcription Factors; D010447:Peptide Hydrolases