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

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

by Yao Li, Kailey M. Slavik, Benjamin R. Morehouse, Carina C. de Oliveira Mann, Kepler Mears, Jingjing Liu, Dmitry Kashin, Frank Schwede, and Philip J. Kranzusch

Posted: February 22, 2023
Server: bioRxiv
DOI: 10.1101/2023.02.22.529553

Abstract

Summary

cGAS (cyclic GMP-AMP synthase) 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 the protein STING and downstream immunity. Here we discover cGAS-like receptors (cGLRs) constitute a major family of pattern recognition receptors in animal innate immunity. Building on recent analysis in Drosophila , we use a bioinformatic approach to identify >3,000 cGLRs present in nearly all metazoan phyla. A forward biochemical screen of 140 animal cGLRs reveals a conserved mechanism of signaling including response to dsDNA and dsRNA ligands and synthesis of alternative nucleotide signals including isomers of cGAMP and cUMP-AMP. Using structural biology, we explain how synthesis of distinct nucleotide signals enables cells to control discrete cGLR-STING signaling pathways. Together our results reveal cGLRs as a widespread family of pattern recognition receptors and establish molecular rules that govern nucleotide signaling in animal immunity.

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PREreview by Mauricio P. Contreras et al. of TSL Preprint Club

Authored by Mauricio P. Contreras, AmirAli Toghani, Daniel Lüdke, and Andrés Posbeyikian of TSL Preprint Club

By Mauricio P. Contreras¹*, Daniel Lüdke¹*, Andrés Posbeyikian¹* and AmirAli Toghani¹*

1: The Sainsbury Laboratory, University of East Anglia, Norwich, UK.
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