IMMUNOLOGY2025™ Conference Recordings-The molecular basis of DNA sensing through the cGAS-STING pathway

The molecular basis of DNA sensing through the cGAS-STING pathway - Pingwei LI

Video Transcription

Video Summary

The speaker reviewed a decade of structural and mechanistic work on the cGAS–STING innate immune pathway. They described how viral DNA activates cGAS to produce cGAMP, which binds STING, drives its oligomerization, and triggers TBK1 and IRF3 to induce type I interferon. The talk highlighted key structures showing that cGAS uses two DNA-binding sites and dimerization to become active, while STING undergoes conformational closure and forms higher-order oligomers. They also explained how phosphorylated STING recruits TBK1 and IRF3 through conserved motifs, leading to downstream signaling. A major new finding was that cGAS is largely nuclear and can be sequestered by nucleosomes, preventing activation by DNA. Finally, they presented a recent structure of ABCC1 exporting cGAMP from cells, showing how extracellular cGAMP can spread immune signaling to neighboring cells.

Keywords

cGAS-STING pathway

innate immune signaling

cGAMP

STING oligomerization

TBK1 IRF3 activation

ABCC1 cGAMP export