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====
==The mouse cGAS catalytic domain binding to human assembled nucleosome==
<StructureSection load='6x59' size='340' side='right'caption='[[6x59]]' scene=''>
<StructureSection load='6x59' size='340' side='right'caption='[[6x59]], [[Resolution|resolution]] 2.98&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>
<table><tr><td colspan='2'>[[6x59]] is a 11 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6X59 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6X59 FirstGlance]. <br>
</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6x59 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6x59 OCA], [https://pdbe.org/6x59 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6x59 RCSB], [https://www.ebi.ac.uk/pdbsum/6x59 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6x59 ProSAT]</span></td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.98&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6x59 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6x59 OCA], [https://pdbe.org/6x59 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6x59 RCSB], [https://www.ebi.ac.uk/pdbsum/6x59 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6x59 ProSAT]</span></td></tr>
</table>
</table>
== Function ==
[https://www.uniprot.org/uniprot/H32_HUMAN H32_HUMAN]
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Pathogen-derived nucleic acids induce potent innate immune responses(1-6). Cyclic GMP-AMP synthase (cGAS) is a dsDNA sensor that catalyzes the synthesis of a cyclic dinucleotide cGAMP, which mediates the induction of type I interferons through the STING-TBK1-IRF3 signaling axis(7-11). It was widely accepted that cGAS is not reactive to self-DNA due to its cytosolic localization(2,12,13). However, recent studies revealed that cGAS is mostly localized in the nucleus and tight nuclear tethering keeps cGAS inactive(14-18). Here we show that cGAS binds to nucleosomes with nanomolar affinity and nucleosome binding potently inhibits the catalytic activity of cGAS. To elucidate the molecular basis of cGAS inactivation by nuclear tethering, we have determined the structure of mouse cGAS bound to human nucleosome by cryo-EM. The structure shows that cGAS binds to a negatively charged acidic patch formed by histone H2A and H2B via its second DNA binding site(19). High affinity nucleosome binding blocks dsDNA binding and keeps cGAS in an inactive conformation. Mutations of cGAS that disrupt nucleosome binding dramatically affect cGAS mediated signaling in cells.
The Molecular Basis of Tight Nuclear Tethering and Inactivation of cGAS.,Zhao B, Xu P, Rowlett CM, Jing T, Shinde O, Lei Y, West AP, Liu WR, Li P Nature. 2020 Sep 10. pii: 10.1038/s41586-020-2749-z. doi:, 10.1038/s41586-020-2749-z. PMID:32911481<ref>PMID:32911481</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6x59" style="background-color:#fffaf0;"></div>
==See Also==
*[[Cyclic GMP-AMP synthase 3D synthase|Cyclic GMP-AMP synthase 3D synthase]]
*[[Histone 3D structures|Histone 3D structures]]
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Z-disk]]
[[Category: Mus musculus]]
[[Category: Baoyu Z]]
[[Category: Pengbiao X]]
[[Category: Pingwei L]]
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