Cryo-EM structures of STING reveal its mechanism of activation by cyclic GMP-AMP.

ABSTRACT: Infections by pathogens that contain DNA trigger the production of type-I interferons and inflammatory cytokines through cyclic GMP-AMP synthase, which produces 2'3'-cyclic GMP-AMP (cGAMP) that binds to and activates stimulator of interferon genes (STING; also known as TMEM173, MITA, ERIS and MPYS)^1-8. STING is an endoplasmic-reticulum membrane protein that contains four transmembrane helices followed by a cytoplasmic ligand-binding and signalling domain^9-13. The cytoplasmic domain of STING forms a dimer, which undergoes a conformational change upon binding to cGAMP^9,14. However, it remains unclear how this conformational change leads to STING activation. Here we present cryo-electron microscopy structures of full-length STING from human and chicken in the

SUBMITTER: Shang G 

PROVIDER: S-EPMC6859894 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature