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Cell. 2014 Aug 28;158(5):1136-1147. doi: 10.1016/j.cell.2014.07.022.

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

Author information

1
Department of Molecular Microbiology, John Innes Centre, Norwich Research Park, Norwich NR4 7UH, UK.
2
Department of Biochemistry, Duke University School of Medicine, Durham, NC 27710, USA.
3
Department of Molecular Microbiology, John Innes Centre, Norwich Research Park, Norwich NR4 7UH, UK. Electronic address: mark.buttner@jic.ac.uk.

Abstract

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.

PMID:
25171413
PMCID:
PMC4151990
DOI:
10.1016/j.cell.2014.07.022
[Indexed for MEDLINE]
Free PMC Article

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