8TRG

Structure of full-length LexA bound to a RecA filament

This is a non-PDB format compatible entry.

Summary for 8TRG

• Entry DOI: 10.2210/pdb8trg/pdb
• EMDB information: 41579
• Descriptor: Protein RecA, LexA repressor, DNA (27-MER), ... (5 entities in total)
• Functional Keywords: damage response, signal transduction, signaling protein, signaling protein-dna complex, signaling protein/dna
• Biological source: Escherichia coli; More
• Total number of polymer chains: 11
• Total formula weight: 387181.08

Authors

Cory, M.B.,Li, A.,Kohli, R.M. (deposition date: 2023-08-09, release date: 2023-11-15, Last modification date: 2024-10-30)

Primary citation

Cory, M.B.,Li, A.,Hurley, C.M.,Carman, P.J.,Pumroy, R.A.,Hostetler, Z.M.,Perez, R.M.,Venkatesh, Y.,Li, X.,Gupta, K.,Petersson, E.J.,Kohli, R.M.
The LexA-RecA* structure reveals a cryptic lock-and-key mechanism for SOS activation.
Nat.Struct.Mol.Biol., 31:1522-1531, 2024

PubMed Abstract: 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.

PubMed: 38755298
DOI: 10.1038/s41594-024-01317-3

Experimental method

ELECTRON MICROSCOPY (2.93 Å)