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

Avatar
Poster
Voices Powered byElevenlabs logo
Connected to paperThis paper is a preprint and has not been certified by peer review

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

Authors

Cory, M. B.; Li, A.; Hurley, C. M.; Carman, P. J.; Pumroy, R. A.; Hostetler, Z. M.; Venkatesh, Y.; Gupta, K. B.; Petersson, E. J.; Kohli, R. M.

Abstract

The bacterial SOS response plays a key role in adaptation to DNA damage, including that caused by antibiotics. SOS induction begins when activated RecA*, an oligomeric nucleoprotein filament formed on single-stranded DNA, binds to and stimulates autoproteolysis of the repressor LexA. Here, we present the structure of the complete 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 response gene induction. Furthermore, we find that the interface involves three RecA monomers, with a single residue in the central monomer 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.

Follow Us on

0 comments

Add comment