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-Structure paper
Title | The LexA-RecA* structure reveals a cryptic lock-and-key mechanism for SOS activation. |
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Journal, issue, pages | Nat Struct Mol Biol, Year 2024 |
Publish date | May 16, 2024 |
Authors | 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 / |
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 ...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. |
External links | Nat Struct Mol Biol / PubMed:38755298 |
Methods | EM (helical sym.) |
Resolution | 2.93 Å |
Structure data | EMDB-41579, PDB-8trg: |
Chemicals | ChemComp-AGS: ChemComp-MG: |
Source |
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Keywords | SIGNALING PROTEIN/DNA / Damage response / signal transduction / SIGNALING PROTEIN / SIGNALING PROTEIN-DNA complex |