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| | ==X-ray crystal structure of human cyclic GMP-AMP synthase (cGAS)== | | ==X-ray crystal structure of human cyclic GMP-AMP synthase (cGAS)== |
| - | <StructureSection load='4km5' size='340' side='right' caption='[[4km5]], [[Resolution|resolution]] 2.50Å' scene=''> | + | <StructureSection load='4km5' size='340' side='right'caption='[[4km5]], [[Resolution|resolution]] 2.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4km5]] 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=4KM5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4KM5 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4km5]] is a 1 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=4KM5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4KM5 FirstGlance]. <br> |
| - | </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> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='gene'><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 id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4km5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4km5 OCA], [https://pdbe.org/4km5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4km5 RCSB], [https://www.ebi.ac.uk/pdbsum/4km5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4km5 ProSAT]</span></td></tr> |
| - | <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=4km5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4km5 OCA], [http://pdbe.org/4km5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4km5 RCSB], [http://www.ebi.ac.uk/pdbsum/4km5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4km5 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[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> | + | [https://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> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 4km5" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 4km5" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Cyclic GMP-AMP synthase 3D synthase|Cyclic GMP-AMP synthase 3D synthase]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Berger, J M]] | + | [[Category: Large Structures]] |
| - | [[Category: Doudna, J A]] | + | [[Category: Berger JM]] |
| - | [[Category: Kranzusch, P J]] | + | [[Category: Doudna JA]] |
| - | [[Category: Lee, A S.Y]] | + | [[Category: Kranzusch PJ]] |
| - | [[Category: Cytoplasmic]] | + | [[Category: Lee ASY]] |
| - | [[Category: Dna]]
| + | |
| - | [[Category: Dna sensor]]
| + | |
| - | [[Category: Innate immunity]]
| + | |
| - | [[Category: Nucleotidyl transferase]]
| + | |
| - | [[Category: Transferase]]
| + | |
| - | [[Category: Zinc finger]]
| + | |
| Structural highlights
Function
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.[1] [2]
Publication Abstract from PubMed
Innate immune recognition of foreign nucleic acids induces protective interferon responses. Detection of cytosolic DNA triggers downstream immune signaling through activation of cyclic GMP-AMP synthase (cGAS). We report here the crystal structure of human cGAS, revealing an unanticipated zinc-ribbon DNA-binding domain appended to a core enzymatic nucleotidyltransferase scaffold. The catalytic core of cGAS is structurally homologous to the RNA-sensing enzyme, 2'-5' oligo-adenylate synthase (OAS), and divergent C-terminal domains account for specific ligand-activation requirements of each enzyme. We show that the cGAS zinc ribbon is essential for STING-dependent induction of the interferon response and that conserved amino acids displayed within the intervening loops are required for efficient cytosolic DNA recognition. These results demonstrate that cGAS and OAS define a family of innate immunity sensors and that structural divergence from a core nucleotidyltransferase enables second-messenger responses to distinct foreign nucleic acids.
Structure of Human cGAS Reveals a Conserved Family of Second-Messenger Enzymes in Innate Immunity.,Kranzusch PJ, Lee AS, Berger JM, Doudna JA Cell Rep. 2013 May 30;3(5):1362-8. doi: 10.1016/j.celrep.2013.05.008. Epub 2013, May 23. PMID:23707061[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Schoggins JW, Wilson SJ, Panis M, Murphy MY, Jones CT, Bieniasz P, Rice CM. A diverse range of gene products are effectors of the type I interferon antiviral response. Nature. 2011 Apr 28;472(7344):481-5. doi: 10.1038/nature09907. Epub 2011 Apr 10. PMID:21478870 doi:10.1038/nature09907
- ↑ Sun L, Wu J, Du F, Chen X, Chen ZJ. Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway. Science. 2013 Feb 15;339(6121):786-91. doi: 10.1126/science.1232458. Epub 2012, Dec 20. PMID:23258413 doi:10.1126/science.1232458
- ↑ Kranzusch PJ, Lee AS, Berger JM, Doudna JA. Structure of Human cGAS Reveals a Conserved Family of Second-Messenger Enzymes in Innate Immunity. Cell Rep. 2013 May 30;3(5):1362-8. doi: 10.1016/j.celrep.2013.05.008. Epub 2013, May 23. PMID:23707061 doi:10.1016/j.celrep.2013.05.008
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