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| | ==Structure of mouse cGAS bound to an 18bp DNA and cGAS product== | | ==Structure of mouse cGAS bound to an 18bp DNA and cGAS product== |
| - | <StructureSection load='4lez' size='340' side='right' caption='[[4lez]], [[Resolution|resolution]] 2.36Å' scene=''> | + | <StructureSection load='4lez' size='340' side='right'caption='[[4lez]], [[Resolution|resolution]] 2.36Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4lez]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4LEZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4LEZ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4lez]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4LEZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4LEZ FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1SY:CGAMP'>1SY</scene>, <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=1SY:CGAMP'>1SY</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4lev|4lev]], [[4lew|4lew]], [[4ley|4ley]]</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=4lez FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4lez OCA], [https://pdbe.org/4lez PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4lez RCSB], [https://www.ebi.ac.uk/pdbsum/4lez PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4lez ProSAT]</span></td></tr> |
| - | <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 LK3 transgenic mice])</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=4lez FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4lez OCA], [http://pdbe.org/4lez PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4lez RCSB], [http://www.ebi.ac.uk/pdbsum/4lez PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4lez ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[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. | + | [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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | ==See Also== | | ==See Also== |
| - | *[[Cyclic GMP-AMP synthase|Cyclic GMP-AMP synthase]] | + | *[[Cyclic GMP-AMP synthase 3D synthase|Cyclic GMP-AMP synthase 3D synthase]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Large Structures]] |
| - | [[Category: Li, P]] | + | [[Category: Mus musculus]] |
| - | [[Category: Dna sensor]] | + | [[Category: Li P]] |
| - | [[Category: Ntase]]
| + | |
| - | [[Category: Transferase-dna complex]]
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| Structural highlights
Function
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.
Publication Abstract from PubMed
Cyclic GMP-AMP synthase (cGAS) is a cytosolic DNA sensor mediating innate antimicrobial immunity. It catalyzes the synthesis of a noncanonical cyclic dinucleotide, 2',5' cGAMP, that binds to STING and mediates the activation of TBK1 and IRF-3. Activated IRF-3 translocates to the nucleus and initiates the transcription of the IFN-beta gene. The structure of mouse cGAS bound to an 18 bp dsDNA revealed that cGAS interacts with dsDNA through two binding sites, forming a 2:2 complex. Enzyme assays and IFN-beta reporter assays of cGAS mutants demonstrated that interactions at both DNA binding sites are essential for cGAS activation. Mutagenesis and DNA binding studies showed that the two sites bind dsDNA cooperatively and that site B plays a critical role in DNA binding. The structure of mouse cGAS bound to dsDNA and 2',5' cGAMP provided insight into the catalytic mechanism of cGAS. These results demonstrated that cGAS is activated by dsDNA-induced oligomerization.
Cyclic GMP-AMP Synthase Is Activated by Double-Stranded DNA-Induced Oligomerization.,Li X, Shu C, Yi G, Chaton CT, Shelton CL, Diao J, Zuo X, Kao CC, Herr AB, Li P Immunity. 2013 Dec 12;39(6):1019-31. doi: 10.1016/j.immuni.2013.10.019. PMID:24332030[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Li X, Shu C, Yi G, Chaton CT, Shelton CL, Diao J, Zuo X, Kao CC, Herr AB, Li P. Cyclic GMP-AMP Synthase Is Activated by Double-Stranded DNA-Induced Oligomerization. Immunity. 2013 Dec 12;39(6):1019-31. doi: 10.1016/j.immuni.2013.10.019. PMID:24332030 doi:http://dx.doi.org/10.1016/j.immuni.2013.10.019
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