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Publication Abstract from PubMed

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-sigma (RsiG) to bind and sequester a sporulation-specific sigma factor (sigma(WhiG)). We present the structure of the RsiG-(c-di-GMP)2-sigma(WhiG) complex, revealing an unusual, partially intercalated c-di-GMP dimer bound at the RsiG-sigma(WhiG) interface. RsiG binds c-di-GMP in the absence of sigma(WhiG), 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 sigma(WhiG). These findings reveal a newly described control mechanism for sigma-anti-sigma complex formation and establish c-di-GMP as the central integrator of Streptomyces development.

c-di-GMP Arms an Anti-sigma to Control Progression of Multicellular Differentiation in Streptomyces.,Gallagher KA, Schumacher MA, Bush MJ, Bibb MJ, Chandra G, Holmes NA, Zeng W, Henderson M, Zhang H, Findlay KC, Brennan RG, Buttner MJ Mol Cell. 2019 Nov 27. pii: S1097-2765(19)30835-4. doi:, 10.1016/j.molcel.2019.11.006. PMID:31810759^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.