8EFN

Structure of Sp-STING3 from Stylophora pistillata coral in complex with 3',3'-cGAMP

Summary for 8EFN

• Entry DOI: 10.2210/pdb8efn/pdb
• Descriptor: Stimulator of interferon genes protein, 1,2-ETHANEDIOL, 2-amino-9-[(2R,3R,3aS,5R,7aR,9R,10R,10aS,12R,14aR)-9-(6-amino-9H-purin-9-yl)-3,5,10,12-tetrahydroxy-5,12-dioxidooctahydro-2H,7H-difuro[3,2-d:3',2'-j][1,3,7,9,2,8]tetraoxadiphosphacyclododecin-2-yl]-1,9-dihydro-6H-purin-6-one, ... (4 entities in total)
• Functional Keywords: immune receptor, cgas-sting, coral, innate immunity, immune system
• Biological source: Stylophora pistillata
• Total number of polymer chains: 2
• Total formula weight: 43697.89

Authors

Li, Y.,Slavik, K.M.,Morehouse, B.R.,Mears, K.,Kranzusch, P.J. (deposition date: 2022-09-08, release date: 2023-07-05, Last modification date: 2023-10-25)

Primary citation

Li, Y.,Slavik, K.M.,Toyoda, H.C.,Morehouse, B.R.,de Oliveira Mann, C.C.,Elek, A.,Levy, S.,Wang, Z.,Mears, K.S.,Liu, J.,Kashin, D.,Guo, X.,Mass, T.,Sebe-Pedros, A.,Schwede, F.,Kranzusch, P.J.
cGLRs are a diverse family of pattern recognition receptors in innate immunity.
Cell, 186:3261-3276.e20, 2023

PubMed Abstract: Cyclic GMP-AMP synthase (cGAS) is an enzyme in human cells that controls an immune response to cytosolic DNA. Upon binding DNA, cGAS synthesizes a nucleotide signal 2'3'-cGAMP that activates STING-dependent downstream immunity. Here, we discover that cGAS-like receptors (cGLRs) constitute a major family of pattern recognition receptors in innate immunity. Building on recent analysis in Drosophila, we identify >3,000 cGLRs present in nearly all metazoan phyla. A forward biochemical screening of 150 animal cGLRs reveals a conserved mechanism of signaling including response to dsDNA and dsRNA ligands and synthesis of isomers of the nucleotide signals cGAMP, c-UMP-AMP, and c-di-AMP. Combining structural biology and in vivo analysis in coral and oyster animals, we explain how synthesis of distinct nucleotide signals enables cells to control discrete cGLR-STING signaling pathways. Our results reveal cGLRs as a widespread family of pattern recognition receptors and establish molecular rules that govern nucleotide signaling in animal immunity.

PubMed: 37379839
DOI: 10.1016/j.cell.2023.05.038

Experimental method

X-RAY DIFFRACTION (1.73 Å)