Structure of STING bound to c-di-GMP Reveals the Mechanism of Cyclic Dinucleotide Recognition by the Immune System

STING, stimulator of interferon genes, is an innate immune sensor of cyclic dinucleotides that regulates the induction of type I interferons. STING C-terminal domain forms a V-shaped dimer and binds a c-di-GMP molecule at the dimer interface through direct and solvent-mediated hydrogen bonds. The guanine bases of c-di-GMP stack against the phenolic rings of a conserved tyrosine residue. Mutations at the c-di-GMP binding surface reduce nucleotide binding and affect signaling.