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4mkp

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{{STRUCTURE_4mkp| PDB=4mkp | SCENE= }}
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==Crystal structure of human cGAS apo form==
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===Crystal structure of human cGAS apo form===
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<StructureSection load='4mkp' size='340' side='right' caption='[[4mkp]], [[Resolution|resolution]] 1.95&Aring;' scene=''>
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{{ABSTRACT_PUBMED_24116191}}
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== Structural highlights ==
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<table><tr><td colspan='2'>[[4mkp]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4MKP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4MKP FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MB21D1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4mkp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mkp OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4mkp RCSB], [http://www.ebi.ac.uk/pdbsum/4mkp PDBsum]</span></td></tr>
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</table>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The detection of cytosolic DNA, derived from pathogens or host cells, by cytosolic receptors is essential for appropriate host immune responses. Cyclic GMP-AMP synthase (cGAS) is a newly identified cytosolic DNA receptor that produces cyclic GMP-AMP, which activates stimulator of interferon genes (STING), resulting in TBK1-IRF3 pathway activation followed by the production of type I interferons. Here we report the crystal structure of human cGAS. The structure revealed that a cluster of lysine and arginine residues forms the positively charged DNA binding surface of human cGAS, which is important for the STING-dependent immune activation. A structural comparison with other previously determined cGASs and our functional analyses suggested that a conserved zinc finger motif and a leucine residue on the DNA binding surface are crucial for the DNA-specific immune response of human cGAS, consistent with previous work. These structural features properly orient the DNA binding to cGAS, which is critical for DNA-induced cGAS activation and STING-dependent immune activation. Furthermore, we showed that the cGAS-induced activation of STING also involves the activation of the NF-kappaB and IRF3 pathways. Our results indicated that cGAS is a DNA sensor that efficiently activates the host immune system by inducing two distinct pathways.
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==Function==
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Structural and Functional Analyses of DNA-Sensing and Immune Activation by Human cGAS.,Kato K, Ishii R, Goto E, Ishitani R, Tokunaga F, Nureki O PLoS One. 2013 Oct 7;8(10):e76983. doi: 10.1371/journal.pone.0076983. PMID:24116191<ref>PMID:24116191</ref>
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[[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>
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[4mkp]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4MKP OCA].
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</div>
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==Reference==
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==See Also==
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<ref group="xtra">PMID:024116191</ref><references group="xtra"/><references/>
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*[[Cyclic GMP-AMP synthase|Cyclic GMP-AMP synthase]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Ishii, R.]]
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[[Category: Ishii, R]]
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[[Category: Ishitani, R.]]
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[[Category: Ishitani, R]]
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[[Category: Kato, K.]]
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[[Category: Kato, K]]
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[[Category: Nureki, O.]]
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[[Category: Nureki, O]]
[[Category: Nucleotidyltransferase]]
[[Category: Nucleotidyltransferase]]
[[Category: Transferase]]
[[Category: Transferase]]

Revision as of 15:33, 21 December 2014

Crystal structure of human cGAS apo form

4mkp, resolution 1.95Å

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