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| <SX load='6cb8' size='340' side='right' viewer='molstar' caption='[[6cb8]], [[Resolution|resolution]] 3.80Å' scene=''> | | <SX load='6cb8' size='340' side='right' viewer='molstar' caption='[[6cb8]], [[Resolution|resolution]] 3.80Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[6cb8]] is a 1 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=6CB8 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6CB8 FirstGlance]. <br> | | <table><tr><td colspan='2'>[[6cb8]] is a 1 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=6CB8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6CB8 FirstGlance]. <br> |
| </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CDL:CARDIOLIPIN'>CDL</scene></td></tr> | | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.8Å</td></tr> |
| <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Gsdma3, Gsdm3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr> | | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CDL:CARDIOLIPIN'>CDL</scene></td></tr> |
| <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6cb8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cb8 OCA], [http://pdbe.org/6cb8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6cb8 RCSB], [http://www.ebi.ac.uk/pdbsum/6cb8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6cb8 ProSAT]</span></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=6cb8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6cb8 OCA], [https://pdbe.org/6cb8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6cb8 RCSB], [https://www.ebi.ac.uk/pdbsum/6cb8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6cb8 ProSAT]</span></td></tr> |
| </table> | | </table> |
| == Disease == | | == Disease == |
| [[http://www.uniprot.org/uniprot/GSDA3_MOUSE GSDA3_MOUSE]] Defects in Gsdma3 are the cause of a number of alopecia phenotypes, bareskin (Bsk), defolliculated (Dfl), finnegan (Fgn) reduced coat 2 (Rco2), Rex-denuded (Re-den) and recombination induced mutation 3 (Rim3). These are dominant conditions characterized by loss of hair.<ref>PMID:15475261</ref> <ref>PMID:15737203</ref> <ref>PMID:17572385</ref> | | [https://www.uniprot.org/uniprot/GSDA3_MOUSE GSDA3_MOUSE] Defects in Gsdma3 are the cause of a number of alopecia phenotypes, bareskin (Bsk), defolliculated (Dfl), finnegan (Fgn) reduced coat 2 (Rco2), Rex-denuded (Re-den) and recombination induced mutation 3 (Rim3). These are dominant conditions characterized by loss of hair.<ref>PMID:15475261</ref> <ref>PMID:15737203</ref> <ref>PMID:17572385</ref> |
| == Function == | | == Function == |
| [[http://www.uniprot.org/uniprot/GSDA3_MOUSE GSDA3_MOUSE]] Upon activation, mediates pyroptosis (PubMed:26375003). May play a role in the transition from catagen to telogen at the end of hair follicle morphogenesis (PubMed:15475261).<ref>PMID:15475261</ref> <ref>PMID:26375003</ref> | | [https://www.uniprot.org/uniprot/GSDA3_MOUSE GSDA3_MOUSE] Upon activation, mediates pyroptosis (PubMed:26375003). May play a role in the transition from catagen to telogen at the end of hair follicle morphogenesis (PubMed:15475261).<ref>PMID:15475261</ref> <ref>PMID:26375003</ref> |
| <div style="background-color:#fffaf0;">
| |
| == Publication Abstract from PubMed ==
| |
| Gasdermins mediate inflammatory cell death after cleavage by caspases or other, unknown enzymes. The cleaved N-terminal fragments bind to acidic membrane lipids to form pores, but the mechanism of pore formation remains unresolved. Here we present the cryo-electron microscopy structures of the 27-fold and 28-fold single-ring pores formed by the N-terminal fragment of mouse GSDMA3 (GSDMA3-NT) at 3.8 and 4.2 A resolutions, and of a double-ring pore at 4.6 A resolution. In the 27-fold pore, a 108-stranded anti-parallel beta-barrel is formed by two beta-hairpins from each subunit capped by a globular domain. We identify a positively charged helix that interacts with the acidic lipid cardiolipin. GSDMA3-NT undergoes radical conformational changes upon membrane insertion to form long, membrane-spanning beta-strands. We also observe an unexpected additional symmetric ring of GSDMA3-NT subunits that does not insert into the membrane in the double-ring pore, which may represent a pre-pore state of GSDMA3-NT. These structures provide a basis that explains the activities of several mutant gasdermins, including defective mutants that are associated with cancer.
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| Cryo-EM structure of the gasdermin A3 membrane pore.,Ruan J, Xia S, Liu X, Lieberman J, Wu H Nature. 2018 May;557(7703):62-67. doi: 10.1038/s41586-018-0058-6. Epub 2018 Apr, 25. PMID:29695864<ref>PMID:29695864</ref>
| | ==See Also== |
| | | *[[Gasdermin|Gasdermin]] |
| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| | *[[Gasdermin 3D structures|Gasdermin 3D structures]] |
| </div>
| |
| <div class="pdbe-citations 6cb8" style="background-color:#fffaf0;"></div>
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| == References == | | == References == |
| <references/> | | <references/> |
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| </SX> | | </SX> |
| [[Category: Large Structures]] | | [[Category: Large Structures]] |
| [[Category: Lk3 transgenic mice]] | | [[Category: Mus musculus]] |
| [[Category: Ruan, J]] | | [[Category: Ruan J]] |
| [[Category: Wu, H]] | | [[Category: Wu H]] |
| [[Category: Immune system]]
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| [[Category: Pore forming protein]]
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| [[Category: Pyroptosis]]
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