Tetrameric c-di-GMP mediates effective transcription factor dimerization to control Streptomyces development.

Journal Article (Journal Article)

The cyclic dinucleotide c-di-GMP is a signaling molecule with diverse functions in cellular physiology. Here, we report that c-di-GMP can assemble into a tetramer that mediates the effective dimerization of a transcription factor, BldD, which controls the progression of multicellular differentiation in sporulating actinomycete bacteria. BldD represses expression of sporulation genes during vegetative growth in a manner that depends on c-di-GMP-mediated dimerization. Structural and biochemical analyses show that tetrameric c-di-GMP links two subunits of BldD through their C-terminal domains, which are otherwise separated by ~10 Å and thus cannot effect dimerization directly. Binding of the c-di-GMP tetramer by BldD is selective and requires a bipartite RXD-X8-RXXD signature. The findings indicate a unique mechanism of protein dimerization and the ability of nucleotide signaling molecules to assume alternative oligomeric states to effect different functions.

Full Text

Duke Authors

Cited Authors

  • Tschowri, N; Schumacher, MA; Schlimpert, S; Chinnam, NB; Findlay, KC; Brennan, RG; Buttner, MJ

Published Date

  • August 28, 2014

Published In

Volume / Issue

  • 158 / 5

Start / End Page

  • 1136 - 1147

PubMed ID

  • 25171413

Pubmed Central ID

  • PMC4151990

Electronic International Standard Serial Number (EISSN)

  • 1097-4172

Digital Object Identifier (DOI)

  • 10.1016/j.cell.2014.07.022


  • eng

Conference Location

  • United States