4k97

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{{STRUCTURE_4k97| PDB=4k97 | SCENE= }}
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==Structure of Ternary Complex of cGAS with dsDNA and Bound ATP==
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===Structure of Ternary Complex of cGAS with dsDNA and Bound ATP===
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<StructureSection load='4k97' size='340' side='right' caption='[[4k97]], [[Resolution|resolution]] 2.41&Aring;' scene=''>
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{{ABSTRACT_PUBMED_23647843}}
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== Structural highlights ==
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<table><tr><td colspan='2'>[[4k97]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4K97 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4K97 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=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4k96|4k96]], [[4k8v|4k8v]], [[4k98|4k98]], [[4k99|4k99]], [[4k9a|4k9a]], [[4k9b|4k9b]]</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=10090 Mus musculus])</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=4k97 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4k97 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4k97 RCSB], [http://www.ebi.ac.uk/pdbsum/4k97 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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Recent studies identified cyclic GMP-AMP (cGAMP) as a metazoan second messenger triggering an interferon response. cGAMP is generated from GTP and ATP by cytoplasmic dsDNA sensor cGAMP synthase (cGAS). We combined structural, chemical, biochemical, and cellular assays to demonstrate that this second messenger contains G(2',5')pA and A(3',5')pG phosphodiester linkages, designated c[G(2',5')pA(3',5')p]. We show that, upon dsDNA binding, cGAS is activated through conformational transitions, resulting in formation of a catalytically competent and accessible nucleotide-binding pocket for generation of c[G(2',5')pA(3',5')p]. We demonstrate that cyclization occurs in a stepwise manner through initial generation of 5'-pppG(2',5')pA prior to cyclization to c[G(2',5')pA(3',5')p], with the latter positioned precisely in the catalytic pocket. Mutants of cGAS dsDNA-binding or catalytic pocket residues exhibit reduced or abrogated activity. Our studies have identified c[G(2',5')pA(3',5')p] as a founding member of a family of metazoan 2',5'-containing cyclic heterodinucleotide second messengers distinct from bacterial 3',5' cyclic dinucleotides.
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==Function==
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Cyclic [G(2',5')pA(3',5')p] is the metazoan second messenger produced by DNA-activated cyclic GMP-AMP synthase.,Gao P, Ascano M, Wu Y, Barchet W, Gaffney BL, Zillinger T, Serganov AA, Liu Y, Jones RA, Hartmann G, Tuschl T, Patel DJ Cell. 2013 May 23;153(5):1094-107. doi: 10.1016/j.cell.2013.04.046. Epub 2013 May, 3. PMID:23647843<ref>PMID:23647843</ref>
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[[http://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.
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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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[[4k97]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4K97 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:023647843</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: Mus musculus]]
[[Category: Mus musculus]]
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[[Category: Gao, P.]]
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[[Category: Gao, P]]
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[[Category: Patel, D J.]]
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[[Category: Patel, D J]]
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[[Category: Wu, Y.]]
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[[Category: Wu, Y]]
[[Category: Nucleotidyltransferase fold]]
[[Category: Nucleotidyltransferase fold]]
[[Category: Transferase-dna complex]]
[[Category: Transferase-dna complex]]

Revision as of 15:18, 21 December 2014

Structure of Ternary Complex of cGAS with dsDNA and Bound ATP

4k97, resolution 2.41Å

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