Extended Data Fig. 6: Interaction of cGAS1 with NCP1 and mechanism of inhibition.

a, Ribbon diagram and a 3D reconstruction of the complex containing cGAS1 (red) and NCP1 (grey, blue). b–f, EM densities (shown as mesh at 4.5σ) for the residues interacting with the nucleosome in cis. Shown are cGAS Loop1, Loop2 and Loop3 interactions in cis with H2A-H2B dimer respectively (b–d) and the interactions of cGAS helix α5 residues with the DNA backbone from NCP1 (e, f). g, Overview of the hcGAS-DNA 2:2 minimal cGAS-DNA active dimer complex to highlight the two distinct DNA-binding surfaces (A-site and B-site) as previously defined¹⁶ (PDB: 4LEY). h, Superposition of the hcGAS-DNA complex (g) onto the cGAS-NCP complex as defined in this work (Fig. 2g). i, Magnified view of the common binding site (B-site) showing the clash of the two DNA strands with the nucleosomal DNA (orange, ligand DNA and grey, nucleosomal DNA).