EMD-22409
2:1 cGAS-nucleosome complex
EMD-22409
Single-particle3.3 Å
Deposition: 06/08/2020Map released: 16/09/2020
Last modified: 06/03/2024
Sample Organism:
Homo sapiens,
synthetic construct,
Mus musculus
Sample: 2:1 cGAS-nucleosome complex
Fitted models: 7joa (Avg. Q-score: 0.474)
Deposition Authors: Boyer JA
,
Spangler CJ
Sample: 2:1 cGAS-nucleosome complex
Fitted models: 7joa (Avg. Q-score: 0.474)
Deposition Authors: Boyer JA
,
Spangler CJ
Structural basis of nucleosome-dependent cGAS inhibition.
Boyer JA ,
Spangler CJ ,
Strauss JD ,
Cesmat AP,
Liu P ,
McGinty RK ,
Zhang Q
(2020) Science , 370 , 450 - 454
,
Spangler CJ ,
Strauss JD ,
Cesmat AP,
Liu P ,
McGinty RK ,
Zhang Q
(2020) Science , 370 , 450 - 454
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.
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.