cGLRs are a diverse family of pattern recognition receptors in innate immunity.

Publication Type:

Journal Article

Authors:

Li, Yao; Slavik, Kailey M; Toyoda, Hunter C; Morehouse, Benjamin R; de Oliveira Mann, Carina C; Elek, Anamaria; Levy, Shani; Wang, Zhenwei; Mears, Kepler S; Liu, Jingjing; Kashin, Dmitry; Guo, Ximing; Mass, Tali; Sebé-Pedrós, Arnau; Schwede, Frank; Kranzusch, Philip J

Source:

Cell, Volume 186, Issue 15, p.3261-3276.e20 (2023)

Keywords:

Animals, DNA, Humans, Immunity, Innate, Nucleotidyltransferases, Receptors, Pattern Recognition, Signal Transduction

Abstract:

<p>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&#39;3&#39;-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 &gt;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&nbsp;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.</p>

PDB: 
8EFM, 8EFN, 8GJW, 8GJX, 8GJY, 8GJZ
Detector: 
PILATUS
EIGER
Beamline: 
24-ID-C
24-ID-E