Crystal structure of the transcriptional repressor DdrO: insight into the metalloprotease/repressor-controlled radiation response in Deinococcus - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue Nucleic Acids Research Année : 2019

Crystal structure of the transcriptional repressor DdrO: insight into the metalloprotease/repressor-controlled radiation response in Deinococcus

David Lemaire
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David Pignol
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Résumé

Exposure to harmful conditions such as radiation and desiccation induce oxidative stress and DNA damage. In radiation-resistant Deinococcus bacteria, the radiation/desiccation response is controlled by two proteins: the XRE family transcriptional repres-sor DdrO and the COG2856 metalloprotease IrrE. The latter cleaves and inactivates DdrO. Here, we report the biochemical characterization and crystal structure of DdrO, which is the first structure of a XRE protein targeted by a COG2856 protein. DdrO is composed of two domains that fold independently and are separated by a flexible linker. The N-terminal domain corresponds to the DNA-binding domain. The C-terminal domain, containing three alpha helices arranged in a novel fold, is required for DdrO dimeriza-tion. Cleavage by IrrE occurs in the loop between the last two helices of DdrO and abolishes dimeriza-tion and DNA binding. The cleavage site is hidden in the DdrO dimer structure, indicating that IrrE cleaves DdrO monomers or that the interaction with IrrE induces a structural change rendering accessible the cleavage site. Predicted COG2856/XRE regulatory protein pairs are found in many bacteria, and available data suggest two different molecular mechanisms for stress-induced gene expression: COG2856 protein-mediated cleavage or inhibition of oligomer-ization without cleavage of the XRE repressor.
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Dates et versions

cea-02315882 , version 1 (05-12-2019)

Identifiants

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Arjan de Groot, Marina I. Siponen, Romaric Magerand, Nicolas Eugenie, Raquel Martin-Arevalillo, et al.. Crystal structure of the transcriptional repressor DdrO: insight into the metalloprotease/repressor-controlled radiation response in Deinococcus. Nucleic Acids Research, 2019, 47 (21), pp.11403-11417. ⟨10.1093/nar/gkz883⟩. ⟨cea-02315882⟩
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