7lt2 | pdb_00007lt2

Structure of a dsRNA-sensing cGAS-like receptor from the beetle Tribolium castaneum

spinqualitylabelsall models 7lt2, resolution 1.58Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7lt2 is a 1 chain structure with sequence from Tribolium castaneum. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.58Å Ligands: MN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function CGLR_TRICA Nucleotidyltransferase that catalyzes the formation of cyclic GMP-AMP (2',3'-cGAMP) from ATP and GTP and plays a key role in innate immunity (PubMed:34261127). Acts as a key sensor of double-stranded RNA (dsRNA), the presence of dsRNA in the cytoplasm being a danger signal that triggers the immune responses (PubMed:34261127). Directly binds dsRNA, activating the nucleotidyltransferase activity, leading to synthesis of 2',3'-cGAMP, a second messenger that binds to and activates Sting, thereby triggering the antiviral immune response via activation of the NF-kappa-B transcription factor Rel (Relish) (By similarity).[UniProtKB:A1ZA55] Publication Abstract from PubMed Cyclic GMP-AMP synthase (cGAS) is a cytosolic DNA sensor that produces the second messenger 2'3'-cGAMP and controls activation of innate immunity in mammalian cells(1-5). Animal genomes typically encode multiple proteins with predicted homology to cGAS(6-10), but the function of these uncharacterized enzymes is unknown. Here we show that cGAS-like receptors (cGLRs) are innate immune sensors capable of recognizing divergent molecular patterns and catalyzing synthesis of distinct nucleotide second messenger signals. Crystal structures of human and insect cGLRs reveal a nucleotidyltransferase signaling core shared with cGAS and a diversified primary ligand-binding surface modified with significant insertions and deletions. We demonstrate that cGLR surface remodeling enables altered ligand specificity and use a forward biochemical screen to identify cGLR1 as a double-stranded RNA sensor in the model organism Drosophila melanogaster. Surprisingly, RNA recognition activates Drosophila cGLR1 to synthesize the novel product cG[3'-5']pA[2'-5']p (3'2'-cGAMP). A crystal structure of Drosophila Stimulator of Interferon Genes (STING) in complex with 3'2'-cGAMP explains selective isomer recognition and we demonstrate that 3'2'-cGAMP induces an enhanced antiviral state in vivo that protects from viral infection. Similar to radiation of Toll-like receptors in pathogen immunity, our results establish cGLRs as a diverse family of metazoan pattern recognition receptors. cGAS-like receptors sense RNA and control 3'2'-cGAMP signaling in Drosophila.,Slavik KM, Morehouse BR, Ragucci AE, Zhou W, Ai X, Chen Y, Li L, Wei Z, Bahre H, Konig M, Seifert R, Lee ASY, Cai H, Imler JL, Kranzusch PJ Nature. 2021 Jul 14. pii: 10.1038/s41586-021-03743-5. doi:, 10.1038/s41586-021-03743-5. PMID:34261127 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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