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New page: '''Unreleased structure''' The entry 8git is ON HOLD Authors: Wu, S., Sohn, J. Description: Structure of Ternary Complex of mouse cGAS with dsDNA and Bound ATP: with 10mM Mg2+ and 1mM ...
 
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'''Unreleased structure'''


The entry 8git is ON HOLD
==Structure of Ternary Complex of mouse cGAS with dsDNA and Bound ATP: with 10mM Mg2+ and 1mM Mn2+==
<StructureSection load='8git' size='340' side='right'caption='[[8git]], [[Resolution|resolution]] 2.72&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8git]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8GIT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8GIT FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.72&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <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=8git FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8git OCA], [https://pdbe.org/8git PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8git RCSB], [https://www.ebi.ac.uk/pdbsum/8git PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8git ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/CGAS_MOUSE CGAS_MOUSE] Nucleotidyltransferase that catalyzes formation of cyclic GMP-AMP (cGAMP) from ATP and GTP and exhibits antiviral activity. Has antiviral activity by acting as a key cytosolic DNA sensor, the presence of DNA in the cytoplasm being a danger signal that triggers the immune responses. Binds cytosolic DNA directly, leading to activation and synthesis of cGAMP, a second messenger that binds to and activates TMEM173/STING, thereby triggering type-I interferon production.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
cGAS activates innate immune responses against cytosolic double-stranded DNA. Here, by determining crystal structures of cGAS at various reaction stages, we report a unifying catalytic mechanism. apo-cGAS assumes an array of inactive conformations and binds NTPs nonproductively. Dimerization-coupled double-stranded DNA-binding then affixes the active site into a rigid lock for productive metal*substrate binding. A web-like network of protein*NTP, intra-NTP, and inter-NTP interactions ensures the stepwise synthesis of 2'-5'/3'-5'-linked cGAMP while discriminating against noncognate NTPs and off-pathway intermediates. One divalent metal is sufficient for productive substrate binding, and capturing the second divalent metal is tightly coupled to nucleotide and linkage specificities, a process which manganese is preferred over magnesium by 100-fold. Additionally, we elucidate how mouse cGAS achieves more stringent NTP and linkage specificities than human cGAS. Together, our results reveal that an adaptable, yet precise lock-and-key-like mechanism underpins cGAS catalysis.


Authors: Wu, S., Sohn, J.
The structural basis for 2'-5'/3'-5'-cGAMP synthesis by cGAS.,Wu S, Gabelli SB, Sohn J Nat Commun. 2024 May 13;15(1):4012. doi: 10.1038/s41467-024-48365-3. PMID:38740774<ref>PMID:38740774</ref>


Description: Structure of Ternary Complex of mouse cGAS with dsDNA and Bound ATP: with 10mM Mg2+ and 1mM Mn2+
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[Category: Unreleased Structures]]
</div>
[[Category: Sohn, J]]
<div class="pdbe-citations 8git" style="background-color:#fffaf0;"></div>
[[Category: Wu, S]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Synthetic construct]]
[[Category: Sohn J]]
[[Category: Wu S]]
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