6nt5

Cryo-EM structure of full-length human STING in the apo stateCryo-EM structure of full-length human STING in the apo state

6nt5, resolution 4.10Å Show:Asymmetric Unit Biological Assembly Structural highlights 6nt5 is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Gene: STING, LOC340061, hCG_1782396 (HUMAN) Experimental data: Check Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed 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 inactive dimeric state (about 80 kDa in size), as well as cGAMP-bound chicken STING in both the dimeric and tetrameric states. The structures show that the transmembrane and cytoplasmic regions interact to form an integrated, domain-swapped dimeric assembly. Closure of the ligand-binding domain, induced by cGAMP, leads to a 180 degrees rotation of the ligand-binding domain relative to the transmembrane domain. This rotation is coupled to a conformational change in a loop on the side of the ligand-binding-domain dimer, which leads to the formation of the STING tetramer and higher-order oligomers through side-by-side packing. This model of STING oligomerization and activation is supported by our structure-based mutational analyses. Cryo-EM structures of STING reveal its mechanism of activation by cyclic GMP-AMP.,Shang G, Zhang C, Chen ZJ, Bai XC, Zhang X Nature. 2019 Mar 6. pii: 10.1038/s41586-019-0998-5. doi:, 10.1038/s41586-019-0998-5. PMID:30842659 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.