Streptomyces are our primary source of antibiotics, produced concomitantly with the transition from vegetative growth to sporulation in a complex developmental life cycle. We previously showed that the signaling molecule c-di-GMP binds BldD, a master repressor, to control initiation of development. Here we demonstrate that c-di-GMP also intervenes later in development to control differentiation of the reproductive hyphae into spores by arming a novel anti-σ (RsiG) to bind and sequester a sporulation-specific σ factor (σWhiG). We present the structure of the RsiG-(c-di-GMP)2-σWhiG complex, revealing an unusual, partially intercalated c-di-GMP dimer bound at the RsiG-σWhiG interface. RsiG binds c-di-GMP in the absence of σWhiG, employing a novel E(X)3S(X)2R(X)3Q(X)3D motif repeated on each helix of a coiled coil. Further studies demonstrate that c-di-GMP is essential for RsiG to inhibit σWhiG. These findings reveal a newly described control mechanism for σ-anti-σ complex formation and establish c-di-GMP as the central integrator of Streptomyces development.

中文翻译：

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c-di-GMP 武装抗 σ 以控制链霉菌中多细胞分化的进程。

链霉菌是我们抗生素的主要来源，在复杂的发育生命周期中伴随着从营养生长到孢子形成的转变而产生。我们之前表明，信号分子 c-di-GMP 与主阻遏物 BldD 结合以控制发育的启动。在这里，我们证明 c-di-GMP 还通过武装一种新型抗 σ (RsiG) 来结合和隔离孢子形成特异性 σ 因子 (σWhiG)，从而在以后的发育过程中进行干预，以控制生殖菌丝向孢子的分化。我们介绍了 RsiG-(c-di-GMP)2-σWhiG 复合物的结构，揭示了一种不寻常的、部分嵌入的 c-di-GMP 二聚体结合在 RsiG-σWhiG 界面上。RsiG 在没有 σWhiG 的情况下结合 c-di-GMP，采用在盘绕线圈的每个螺旋上重复的新型 E(X)3S(X)2R(X)3Q(X)3D 基序。进一步的研究表明，c-di-GMP 对于 RsiG 抑制 σWhiG 是必不可少的。这些发现揭示了一种新描述的 σ-anti-σ 复合物形成的控制机制，并将 c-di-GMP 确立为链霉菌发育的中心整合者。