Applications of cryo-EM in drug development for STING

Abstract

STING is a critical adaptor protein in the cGAS-mediated DNA-sensing innate immune pathway. Binding of the second messenger cGAMP generated by cGAS to STING induces the high-order oligomerization and activation of the STING dimer. STING is a promising target for diseases associated with the cGAS/STING pathway such as cancer and autoimmune diseases. Recent applications of cryo-EM to STING have led to exciting progress in the understanding of its regulatory mechanism. Cryo-EM structures of STING bound to either cGAMP mimetics or novel small molecule ligands not only revealed the action mechanisms of these ligands but also suggested new ways to modulate the activity of STING for therapeutic purposes. Some of these recent studies are highlighted here.