{"doi":"10.1101/2023.02.22.529553","title":"cGLRs are a diverse family of pattern recognition receptors in animal innate immunity","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.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":390681,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9643,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":624012,"name":"Kailey M. Slavik","orcid":"0000-0003-0893-1312","position":1,"is_corresponding":false},{"id":230266,"name":"Benjamin R. Morehouse","orcid":"0000-0003-3352-5463","position":2,"is_corresponding":false},{"id":1019750,"name":"Carina C. de Oliveira Mann","orcid":"0000-0002-1852-9880","position":3,"is_corresponding":false},{"id":1019754,"name":"Kepler Mears","orcid":"0000-0003-2566-3532","position":4,"is_corresponding":false},{"id":331277,"name":"Jingjing Liu","orcid":"0000-0002-3266-7331","position":5,"is_corresponding":false},{"id":243398,"name":"Dmitry Kashin","orcid":null,"position":6,"is_corresponding":false},{"id":239476,"name":"Frank Schwede","orcid":"0000-0002-8185-3392","position":7,"is_corresponding":false},{"id":230272,"name":"Philip J. Kranzusch","orcid":"0000-0002-4943-733X","position":8,"is_corresponding":false},{"id":522383,"name":"Yao Li","orcid":"0000-0003-4741-4799","position":0,"is_corresponding":true}],"reference_count":78,"raw_metadata":null,"created_at":"2026-07-19T01:18:37.743462Z","pmid":"36865129","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}