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Nat Chem Biol. 2017 Mar 22;13(4):350-359. doi: 10.1038/nchembio.2337.

Versatile modes of cellular regulation via cyclic dinucleotides.

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Unité G5 Biologie Structurale de la Sécrétion Bactérienne, UMR 3528 - CNRS, Institut Pasteur, Paris, France.
Structural Biology of Biofilms Group, Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, Université Paris Sud, Gif sur Yvette, France.
Department of Molecular Medicine, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA.


Since the discovery of c-di-GMP almost three decades ago, cyclic dinucleotides (CDNs) have emerged as widely used signaling molecules in most kingdoms of life. The family of second messengers now includes c-di-AMP and distinct versions of mixed cyclic GMP-AMP (cGAMP) compounds. In addition to these nucleotides, a vast number of proteins for the production and turnover of these molecules have been described, as well as effectors that translate the signals into physiological responses. The latter include, but are not limited to, mechanisms for adaptation and survival in prokaryotes, persistence and virulence of bacterial pathogens, and immune responses to viral and bacterial invasion in eukaryotes. In this review, we will focus on recent discoveries and emerging themes that illustrate the ubiquity and versatility of cyclic dinucleotide function at the transcriptional and post-translational levels and, in particular, on insights gained through mechanistic structure-function analyses.

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