Stimulator Of Interferon Genes (STING) protein in bacteria
This model represents the bacterial Stimulator Of Interferon Genes (STING) protein that exhibits clear homology to the cyclic-dinucleotide-binding domain of human STING, and represents a newly identified prokaryotic member of the STING family of receptors. Bacterial STING occurs primarily as a fusion to a Toll/interleukin-1 receptor (TIR, or Toll and IL-1 receptor) adaptor domain, or more rarely are appended to predicted transmembrane segments; TIR domains can function as beta-nicotinamide adenine dinucleotide (NAD+) hydrolases in plant and animal immunity. Bacterial STING proteins define a minimal homodimeric scaffold that selectively responds to cyclic di-GMP synthesized by a neighboring cGAS/DncV-like nucleotidyltransferase (CD-NTase) enzyme. They couple the recognition of cyclic dinucleotides with the formation of protein filaments to drive oligomerization of TIR effector domains and rapid NAD+ cleavage. Structures of Flavobacteriaceae sp. STING (FsSTING) and Capnocytophaga granulosa STING (CgSTING) show that the overall architecture is conserved with metazoan STING; they adopt a canonical V-shaped, homodimeric architecture with a hydrophobic alpha-helix stem. However, bacterial STING proteins are 20% smaller and notably compact. Comparative structural analysis shows that metazoan-specific insertions into the core bacterial STING fold have enabled a switch from direct effector function to regulation of antiviral transcription.
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