7JO9

1:1 cGAS-nucleosome complex

Summary for 7JO9

• Entry DOI: 10.2210/pdb7jo9/pdb
• EMDB information: 22408
• Descriptor: Histone H3.2, Histone H4, Histone H2A type 1, ... (8 entities in total)
• Functional Keywords: cgas, nucleosome, cyclic gmp-amp synthase, dna binding protein-dna-transferase complex, dna binding protein/dna/transferase
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 11
• Total formula weight: 243022.66

Authors

Boyer, J.A.,Spangler, C.J.,Strauss, J.D.,Cesmat, A.P.,Liu, P.,McGinty, R.K.,Zhang, Q. (deposition date: 2020-08-06, release date: 2020-09-16, Last modification date: 2024-03-06)

Primary citation

Boyer, J.A.,Spangler, C.J.,Strauss, J.D.,Cesmat, A.P.,Liu, P.,McGinty, R.K.,Zhang, Q.
Structural basis of nucleosome-dependent cGAS inhibition.
Science, 370:450-454, 2020

PubMed Abstract: Cyclic guanosine monophosphate (GMP)-adenosine monophosphate (AMP) synthase (cGAS) recognizes cytosolic foreign or damaged DNA to activate the innate immune response to infection, inflammatory diseases, and cancer. By 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 uses two conserved arginines to anchor to the nucleosome acidic patch. The nucleosome-binding interface exclusively occupies the strong double-stranded DNA (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.

PubMed: 32913000
DOI: 10.1126/science.abd0609

Experimental method

ELECTRON MICROSCOPY (3.3 Å)