SNAP output for PDB entry 7jo9 [SNAP web server]

PDB-id

7jo9; SNAP-derived features in text and JSON formats; DNAproDB

Class

DNA binding protein-DNA-transferase

Method

cryo-EM (3.3 Å)

Summary

1:1 cgas-nucleosome complex

Reference

Boyer JA, Spangler CJ, Strauss JD, Cesmat AP, Liu P, McGinty RK, Zhang Q (2020): "Structural basis of nucleosome-dependent cGAS inhibition." Science, 370, 450-454. doi: 10.1126/science.abd0609.

Abstract

Cyclic GMP-AMP synthase (cGAS) recognizes cytosolic foreign or damaged DNA to activate the innate immune response to infection, inflammatory diseases, and cancer. In contrast, cGAS reactivity against self-DNA in the nucleus is suppressed by chromatin tethering. We report a 3.3-angstrom-resolution cryo-electron microscopy structure of cGAS in complex with the nucleosome core particle. The structure reveals that cGAS employs two conserved arginines to anchor to the nucleosome acidic patch. The nucleosome binding interface exclusively occupies the strong dsDNA binding surface on cGAS and sterically prevents cGAS from oligomerizing into the functionally active 2:2 cGAS-dsDNA state. These findings provide a structural basis for how cGAS maintains an inhibited state in the nucleus and further exemplify the role of the nucleosome in regulating diverse nuclear protein functions.