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4o6a

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Revision as of 22:01, 5 August 2016

Mouse cyclic GMP-AMP synthase (cGAS) in complex with DNA

Structural highlights

4o6a is a 6 chain structure with sequence from Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	4o67, 4o68, 4o69
Gene:	Mb21d1 (LK3 transgenic mice)
Activity:	Cyclic GMP-AMP synthase, with EC number 2.7.7.86
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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

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.

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^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

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

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4o6a"

@@ Line 1: / Line 1: @@
 ==Mouse cyclic GMP-AMP synthase (cGAS) in complex with DNA==
 <StructureSection load='4o6a' size='340' side='right' caption='[[4o6a]], [[Resolution|resolution]] 1.86&Aring;' scene=''>
@@ Line 7: / Line 8: @@
 <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>
 <tr id='activity'><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 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=4o6a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4o6a OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4o6a RCSB], [http://www.ebi.ac.uk/pdbsum/4o6a PDBsum]</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=4o6a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4o6a OCA], [http://pdbe.org/4o6a PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4o6a RCSB], [http://www.ebi.ac.uk/pdbsum/4o6a PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4o6a ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 19: / Line 20: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4o6a" style="background-color:#fffaf0;"></div>
 ==See Also==

4o6a

From Proteopedia

Revision as of 22:01, 5 August 2016

Mouse cyclic GMP-AMP synthase (cGAS) in complex with DNA

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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