Figure 1. Cyclic dinucleotide (CDN) signaling.
a. Structural overview of the four prevalent cyclic dinucleotides. b. Regulation of CDN signaling. A generic route for the synthesis and degradation of CDNs is shown. Regulatory feedback loops controlling cellular CDN levels have been described in some instances, e.g. for I-site-containing GGDEF domain proteins or the effect of linear di-GMP (pGpG) on PDE-A activity. Note that the listed receptor/effector classes are common examples and not mutually exclusive. Enzymatic activities arise from stand-alone, single-domain proteins or, more typically, from multi-domain proteins, including proteins with both cyclase (i.e. GGDEF) and PDE (i.e. EAL) domains. Regulatory domains (X) determine the mode of enzyme regulation (e.g. environmental sensing, canonical two-component regulation, etc.). Known stimuli include allosteric ligands, post-translational modifications, light, gases, and mechanotransduction. c. Prevalence, biosynthesis and degradation pathways for the four major CDNs.