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-Structure paper
タイトル | Structural basis of nucleosome-dependent cGAS inhibition. |
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ジャーナル・号・ページ | Science, Vol. 370, Issue 6515, Page 450-454, Year 2020 |
掲載日 | 2020年10月23日 |
著者 | Joshua A Boyer / Cathy J Spangler / Joshua D Strauss / Andrew P Cesmat / Pengda Liu / Robert K McGinty / Qi Zhang / |
PubMed 要旨 | Cyclic guanosine monophosphate (GMP)-adenosine monophosphate (AMP) synthase (cGAS) recognizes cytosolic foreign or damaged DNA to activate the innate immune response to infection, inflammatory ...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. |
リンク | Science / PubMed:32913000 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.3 - 3.9 Å |
構造データ | EMDB-22408, PDB-7jo9: EMDB-22409, PDB-7joa: EMDB-22413: |
化合物 | ChemComp-ZN: |
由来 |
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キーワード | DNA Binding Protein/DNA/Transferase / cGAS / nucleosome / cyclic GMP-AMP synthase / DNA Binding Protein-DNA-Transferase complex |