8trg | pdb_00008trg
Structure of full-length LexA bound to a RecA filament
Structural highlights
FunctionRECA_ECOLI Can catalyze the hydrolysis of ATP in the presence of single-stranded DNA, the ATP-dependent uptake of single-stranded DNA by duplex DNA, and the ATP-dependent hybridization of homologous single-stranded DNAs. It interacts with LexA causing its activation and leading to its autocatalytic cleavage.[HAMAP-Rule:MF_00268] Publication Abstract from PubMedThe 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. The LexA-RecA* structure reveals a cryptic lock-and-key mechanism for SOS activation.,Cory MB, Li A, Hurley CM, Carman PJ, Pumroy RA, Hostetler ZM, Perez RM, Venkatesh Y, Li X, Gupta K, Petersson EJ, Kohli RM Nat Struct Mol Biol. 2024 May 16. doi: 10.1038/s41594-024-01317-3. PMID:38755298[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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