c-di-GMP Arms an Anti-σ to Control Progression of Multicellular Differentiation in Streptomyces.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Gallagher, KA; Schumacher, MA; Bush, MJ; Bibb, MJ; Chandra, G; Holmes, NA; Zeng, W; Henderson, M; Zhang, H; Findlay, KC; Brennan, RG; Buttner, MJ

Published Date

  • February 6, 2020

Published In

Volume / Issue

  • 77 / 3

Start / End Page

  • 586 - 599.e6

PubMed ID

  • 31810759

Pubmed Central ID

  • PMC7005675

Electronic International Standard Serial Number (EISSN)

  • 1097-4164

Digital Object Identifier (DOI)

  • 10.1016/j.molcel.2019.11.006


  • eng

Conference Location

  • United States