Fig. 1: Structural remodelling in animal cGLRs enables divergent pattern recognition.
From: cGAS-like receptors sense RNA and control 3′2′-cGAMP signalling in Drosophila
a, Crystal structures and surface electrostatics of hMB21D2 and Tc-cGLR. Structural comparison with the human cGAS (hcGAS)–DNA complex (Protein Data Bank (PDB): 6CTA)14 reveals that cGLRs have a conserved architecture with a nucleotidyltransferase signalling core and a shared primary ligand-binding surface (dashed lines). The purple and green boxes indicate cutaways in b. b, Zoomed-in cutaways highlighting structural insertions and deletions unique to each cGLR. hMB21D2 and Tc-cGLR lack the Zn-ribbon motif present in cGAS (left) and hMB21D2 contains a C-terminal α-helix extension that contacts the central ‘spine’ helix (right). Alterations in the predicted ligand-binding surfaces suggest individual cGLRs are remodelled to recognize different molecular patterns. c, Thin-layer chromatography analysis and quantification of Tc-cGLR reactions in the presence of nucleic acid ligands. Tc-cGLR is specifically activated by dsRNA recognition to synthesize a nucleotide (nt) product. Data are relative to maximum activity and represent the mean ± s.e.m. for n = 3 independent experiments. Ori, origin; Pi, inorganic phosphate; ss, single-stranded.
