View source for 7ccq


==Structure of the 1:1 cGAS-nucleosome complex==
<StructureSection load='7ccq' size='340' side='right'caption='[[7ccq]], [[Resolution|resolution]] 3.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7ccq]] is a 11 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7CCQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7CCQ FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.8&#8491;</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=7ccq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ccq OCA], [https://pdbe.org/7ccq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ccq RCSB], [https://www.ebi.ac.uk/pdbsum/7ccq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ccq ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/H31_HUMAN H31_HUMAN] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Activation of cyclic GMP-AMP synthase (cGAS) through sensing cytosolic double stranded DNA (dsDNA) plays a pivotal role in innate immunity against exogenous infection as well as cellular regulation under stress. Aberrant activation of cGAS induced by self-DNA is related to autoimmune diseases. cGAS accumulates at chromosomes during mitosis or spontaneously in the nucleus. Binding of cGAS to the nucleosome competitively attenuates the dsDNA-mediated cGAS activation, but the molecular mechanism of the attenuation is still poorly understood. Here, we report two cryo-electron microscopy structures of cGAS-nucleosome complexes. The structures reveal that cGAS interacts with the nucleosome as a monomer, forming 1:1 and 2:2 complexes, respectively. cGAS contacts the nucleosomal acidic patch formed by the H2A-H2B heterodimer through the dsDNA-binding site B in both complexes, and could interact with the DNA from the other symmetrically placed nucleosome via the dsDNA-binding site C in the 2:2 complex. The bound nucleosome inhibits the activation of cGAS through blocking the interaction of cGAS with ligand dsDNA and disrupting cGAS dimerization. R236A or R255A mutation of cGAS impairs the binding between cGAS and the nucleosome, and largely relieves the nucleosome-mediated inhibition of cGAS activity. Our study provides structural insights into the inhibition of cGAS activity by the nucleosome, and advances the understanding of the mechanism by which hosts avoid the autoimmune attack caused by cGAS.

Structural basis for nucleosome-mediated inhibition of cGAS activity.,Cao D, Han X, Fan X, Xu RM, Zhang X Cell Res. 2020 Oct 13. pii: 10.1038/s41422-020-00422-4. doi:, 10.1038/s41422-020-00422-4. PMID:33051594<ref>PMID:33051594</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7ccq" 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__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Cao D]]
[[Category: Fan X]]
[[Category: Han X]]
[[Category: Xu RM]]
[[Category: Zhang X]]