title: Structural insight into LexA-RecA* interaction.
abstract: RecA protein is a hallmark for the bacterial response to insults inflicted on DNA. It catalyzes the strand exchange step of homologous recombination and stimulates self-inactivation of the LexA transcriptional repressor. Importantly, by these activities, RecA contributes to the antibiotic resistance of bacteria. An original way to decrease the acquisition of antibiotic resistance would be to block RecA association with LexA. To engineer inhibitors of LexA-RecA complex formation, we have mapped the interaction area between LexA and active RecA-ssDNA filament (RecA*) and generated a three-dimensional model of the complex. The model revealed that one subunit of the LexA dimer wedges into a deep helical groove of RecA*, forming multiple interaction sites along seven consecutive RecA protomers. Based on the model, we predicted that LexA in its DNA-binding conformation also forms a complex with RecA* and that the operator DNA sterically precludes interaction with RecA*, which guides the induction of SOS gene expression. Moreover, the model shows that besides the catalytic C-terminal domain of LexA, its N-terminal DNA-binding domain also interacts with RecA*. Because all the model-based predictions have been confirmed experimentally, the presented model offers a validated insight into the critical step of the bacterial DNA damage response.
authors: Department of Molecular and Biomedical Sciences, JoŽef Stefan Institute, Jamova 39, 1000 Ljubljana, Slovenia, Department of Biology, University of Ljubljana, Biotechnical Faculty, Večna pot 111, 1000 Ljubljana, Slovenia, National Institute of Chemistry, 1000 Ljubljana, Slovenia, Department of Chemistry and Biochemistry, Faculty of Chemistry and Chemical Technology, University of Ljubljana, Aškerčeva 5, SI-1000 Ljubljana, Slovenia and Centre of Excellence for Integrated Approaches in Chemistry and Biology of Proteins, Jamova 39, 1000 Ljubljana, Slovenia.
authors: Lidija
authors: L
authors: Kovačič
authors: Nejc
authors: N
authors: Paulič
authors: Adrijana
authors: A
authors: Leonardi
authors: Vesna
authors: V
authors: Hodnik
authors: Gregor
authors: G
authors: Anderluh
authors: Zdravko
authors: Z
authors: Podlesek
authors: Darja
authors: D
authors: Žgur-Bertok
authors: Igor
authors: I
authors: Križaj
authors: Matej
authors: M
authors: Butala
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009875:Operator Regions, Genetic; D011938:Rec A Recombinases / Q000737:chemistry* / Q000378:metabolism; D012097:Repressor Proteins / Q000737:chemistry* / Q000378:metabolism; D013014:SOS Response, Genetics; D012697:Serine Endopeptidases / Q000737:chemistry* / Q000378:metabolism; D000099160:LexA Repressor Protein
chemical_list: D001426:Bacterial Proteins; D011938:Rec A Recombinases; D012097:Repressor Proteins; D012697:Serine Endopeptidases; D000099160:LexA Repressor Protein
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