4o69: Difference between revisions

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{{STRUCTURE_4o69| PDB=4o69 | SCENE= }}
==Human cyclic GMP-AMP synthase (cGAS) in complex with sulfate ion==
===Human cyclic GMP-AMP synthase (cGAS) in complex with sulfate ion===
<StructureSection load='4o69' size='340' side='right' caption='[[4o69]], [[Resolution|resolution]] 2.25&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4o69]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4O69 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4O69 FirstGlance]. <br>
</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene><br>
<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4o67|4o67]], [[4o68|4o68]], [[4o6a|4o6a]]</td></tr>
<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MB21D1, C6orf150 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
<tr><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Cyclic_GMP-AMP_synthase Cyclic GMP-AMP synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.7.86 2.7.7.86] </span></td></tr>
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4o69 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4o69 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4o69 RCSB], [http://www.ebi.ac.uk/pdbsum/4o69 PDBsum]</span></td></tr>
<table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The presence of DNA in the cytoplasm is a danger signal that triggers immune and inflammatory responses. Cytosolic DNA binds to and activates cyclic GMP-AMP (cGAMP) synthase (cGAS), which produces the second messenger cGAMP. cGAMP binds to the adaptor protein STING and activates a signaling cascade that leads to the production of type I interferons and other cytokines. Here, we report the crystal structures of human cGAS in its apo form, representing its autoinhibited conformation as well as in its cGAMP- and sulfate-bound forms. These structures reveal switch-like conformational changes of an activation loop that result in the rearrangement of the catalytic site. The structure of DNA-bound cGAS reveals a complex composed of dimeric cGAS bound to two molecules of DNA. Functional analyses of cGAS mutants demonstrate that both the protein-protein interface and the two DNA binding surfaces are critical for cGAS activation. These results provide insights into the mechanism of DNA sensing by cGAS.


==Function==
The cytosolic DNA sensor cGAS forms an oligomeric complex with DNA and undergoes switch-like conformational changes in the activation loop.,Zhang X, Wu J, Du F, Xu H, Sun L, Chen Z, Brautigam CA, Zhang X, Chen ZJ Cell Rep. 2014 Feb 13;6(3):421-30. doi: 10.1016/j.celrep.2014.01.003. Epub 2014, Jan 23. PMID:24462292<ref>PMID:24462292</ref>
[[http://www.uniprot.org/uniprot/CGAS_HUMAN CGAS_HUMAN]] 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.<ref>PMID:21478870</ref> <ref>PMID:23258413</ref>


==About this Structure==
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
[[4o69]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4O69 OCA].
</div>
 
== References ==
==Reference==
<references/>
<references group="xtra"/><references/>
__TOC__
</StructureSection>
[[Category: Cyclic GMP-AMP synthase]]
[[Category: Cyclic GMP-AMP synthase]]
[[Category: Human]]
[[Category: Chen, Z.]]
[[Category: Chen, Z.]]
[[Category: Chen, Z J.]]
[[Category: Chen, Z J.]]

Revision as of 13:40, 18 May 2014

Human cyclic GMP-AMP synthase (cGAS) in complex with sulfate ion

4o69, resolution 2.25Å

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