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==Cryo-EM structure of full-length human STING in the apo state== | ==Cryo-EM structure of full-length human STING in the apo state== | ||
<StructureSection load='6nt5' size='340' side='right' | <StructureSection load='6nt5' size='340' side='right'caption='[[6nt5]], [[Resolution|resolution]] 4.10Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6nt5]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NT5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6NT5 FirstGlance]. <br> | <table><tr><td colspan='2'>[[6nt5]] is a 2 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=6NT5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6NT5 FirstGlance]. <br> | ||
</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=6nt5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nt5 OCA], [http://pdbe.org/6nt5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6nt5 RCSB], [http://www.ebi.ac.uk/pdbsum/6nt5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6nt5 ProSAT]</span></td></tr> | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">STING, LOC340061, hCG_1782396 ([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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6nt5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6nt5 OCA], [http://pdbe.org/6nt5 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6nt5 RCSB], [http://www.ebi.ac.uk/pdbsum/6nt5 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6nt5 ProSAT]</span></td></tr> | |||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Infections by pathogens that contain DNA trigger the production of type-I interferons and inflammatory cytokines through cyclic GMP-AMP synthase, which produces 2'3'-cyclic GMP-AMP (cGAMP) that binds to and activates stimulator of interferon genes (STING; also known as TMEM173, MITA, ERIS and MPYS)(1-8). STING is an endoplasmic-reticulum membrane protein that contains four transmembrane helices followed by a cytoplasmic ligand-binding and signalling domain(9-13). The cytoplasmic domain of STING forms a dimer, which undergoes a conformational change upon binding to cGAMP(9,14). However, it remains unclear how this conformational change leads to STING activation. Here we present cryo-electron microscopy structures of full-length STING from human and chicken in the inactive dimeric state (about 80 kDa in size), as well as cGAMP-bound chicken STING in both the dimeric and tetrameric states. The structures show that the transmembrane and cytoplasmic regions interact to form an integrated, domain-swapped dimeric assembly. Closure of the ligand-binding domain, induced by cGAMP, leads to a 180 degrees rotation of the ligand-binding domain relative to the transmembrane domain. This rotation is coupled to a conformational change in a loop on the side of the ligand-binding-domain dimer, which leads to the formation of the STING tetramer and higher-order oligomers through side-by-side packing. This model of STING oligomerization and activation is supported by our structure-based mutational analyses. | |||
Cryo-EM structures of STING reveal its mechanism of activation by cyclic GMP-AMP.,Shang G, Zhang C, Chen ZJ, Bai XC, Zhang X Nature. 2019 Mar 6. pii: 10.1038/s41586-019-0998-5. doi:, 10.1038/s41586-019-0998-5. PMID:30842659<ref>PMID:30842659</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6nt5" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Human]] | |||
[[Category: Large Structures]] | |||
[[Category: Bai, X]] | [[Category: Bai, X]] | ||
[[Category: Chen, Z J]] | [[Category: Chen, Z J]] | ||
Revision as of 11:30, 20 March 2019
Cryo-EM structure of full-length human STING in the apo stateCryo-EM structure of full-length human STING in the apo state
Structural highlights
Publication Abstract from PubMedInfections by pathogens that contain DNA trigger the production of type-I interferons and inflammatory cytokines through cyclic GMP-AMP synthase, which produces 2'3'-cyclic GMP-AMP (cGAMP) that binds to and activates stimulator of interferon genes (STING; also known as TMEM173, MITA, ERIS and MPYS)(1-8). STING is an endoplasmic-reticulum membrane protein that contains four transmembrane helices followed by a cytoplasmic ligand-binding and signalling domain(9-13). The cytoplasmic domain of STING forms a dimer, which undergoes a conformational change upon binding to cGAMP(9,14). However, it remains unclear how this conformational change leads to STING activation. Here we present cryo-electron microscopy structures of full-length STING from human and chicken in the inactive dimeric state (about 80 kDa in size), as well as cGAMP-bound chicken STING in both the dimeric and tetrameric states. The structures show that the transmembrane and cytoplasmic regions interact to form an integrated, domain-swapped dimeric assembly. Closure of the ligand-binding domain, induced by cGAMP, leads to a 180 degrees rotation of the ligand-binding domain relative to the transmembrane domain. This rotation is coupled to a conformational change in a loop on the side of the ligand-binding-domain dimer, which leads to the formation of the STING tetramer and higher-order oligomers through side-by-side packing. This model of STING oligomerization and activation is supported by our structure-based mutational analyses. Cryo-EM structures of STING reveal its mechanism of activation by cyclic GMP-AMP.,Shang G, Zhang C, Chen ZJ, Bai XC, Zhang X Nature. 2019 Mar 6. pii: 10.1038/s41586-019-0998-5. doi:, 10.1038/s41586-019-0998-5. PMID:30842659[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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