Figure 1. STING Cyclic Dinucleotide Recognition Predates Modern Innate Immunity.
(A) Gel-shift assay measuring complex formation between recombinant STING proteins and radiolabeled CDNs. Each panel shows reactions in order: (1) 3′,3′ cAA, (2) 3′,3′ cGAMP, (3) 2′,3′ cGAMP and (4) 3′,3′ cGG. (B) Phylogenetic alignment of animal STING proteins colored by amino-acid conservation. Key CDN interacting residues are indicated. (C) Cartoon schematic of human and anemone STING proteins. Predicted transmembrane domains are indicated in grey, and the crystallized CDN receptor domain is indicated in magenta or blue. Notably, the cterminal tail required for hSTING interferon signaling is absent in nvSTING. (D,E) Crystal structure of apo nvSTING CDN receptor domain in “rotated” and “unrotated” states. Overlaid structures compare the apo nvSTING structures (blue) and apo hSTING (PDB 4F9E) or apo mouse STING (PDB 4KC0) (magenta) revealing conformational dynamics and an ancestrally conserved STING fold. See also Figure S1.
