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.

细菌 SOS 反应在适应 DNA 损伤（包括抗生素引起的基因组应激）中起关键作用。当激活的 RecA*（一种在单链 DNA 上形成的寡聚核蛋白丝）结合并刺激阻遏蛋白 LexA 的自蛋白水解时，SOS 诱导开始。在这里，我们展示了完整的大肠杆菌 SOS 信号复合物的结构，构成与 RecA* 结合的全长 LexA。我们意外地发现了一个广泛的界面，包括 LexA DNA 结合结构域，为有序 SOS 基因诱导提供了新的分子理论。我们进一步发现该界面涉及三个 RecA 亚基，中心啮合亚基中的单个残基充当分子键，插入变构结合口袋以诱导 LexA 切割。鉴于 SOS 激活的促诱变性质，我们的结构和机制见解为开发新的疗法以减缓抗生素耐药性的演变提供了基础。