The LexA-RecA* structure reveals a cryptic lock-and-key mechanism for SOS activation.

The bacterial SOS response plays a key role in adaptation to DNA damage, including genomic stress caused by antibiotics. SOS induction begins when activated RecA*, an oligomeric nucleoprotein filament that forms on single-stranded DNA, binds to and stimulates autoproteolysis of the repressor LexA. Here, we present the structure of the complete Escherichia coli SOS signal complex, constituting full-length LexA bound to RecA*. We uncover an extensive interface unexpectedly including the LexA DNA-binding domain, providing a new molecular rationale for ordered SOS gene induction. We further find that the interface involves three RecA subunits, with a single residue in the central engaged subunit acting as a molecular key, inserting into an allosteric binding pocket to induce LexA cleavage. Given the pro-mutagenic nature of SOS activation, our structural and mechanistic insights provide a foundation for developing new therapeutics to slow the evolution of antibiotic resistance.© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.

Citation

Michael B Cory, Allen Li, Christina M Hurley, Peter J Carman, Ruth A Pumroy, Zachary M Hostetler, Ryann M Perez, Yarra Venkatesh, Xinning Li, Kushol Gupta, E James Petersson, Rahul M Kohli. The LexA-RecA* structure reveals a cryptic lock-and-key mechanism for SOS activation. Nature structural & molecular biology. 2024 May 16

PMID: 38755298

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