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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.
| + | |
| | | | |
| - | 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>
| + | |
| | == 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]]
| + | |
| - | [[Category: Pore forming protein]]
| + | |
| - | [[Category: Pyroptosis]]
| + | |
| Structural highlights
Disease
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.[1] [2] [3]
Function
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).[4] [5]
See Also
References
- ↑ Runkel F, Marquardt A, Stoeger C, Kochmann E, Simon D, Kohnke B, Korthaus D, Wattler F, Fuchs H, Hrabe de Angelis M, Stumm G, Nehls M, Wattler S, Franz T, Augustin M. The dominant alopecia phenotypes Bareskin, Rex-denuded, and Reduced Coat 2 are caused by mutations in gasdermin 3. Genomics. 2004 Nov;84(5):824-35. PMID:15475261 doi:http://dx.doi.org/S0888-7543(04)00179-X
- ↑ Lunny DP, Weed E, Nolan PM, Marquardt A, Augustin M, Porter RM. Mutations in gasdermin 3 cause aberrant differentiation of the hair follicle and sebaceous gland. J Invest Dermatol. 2005 Mar;124(3):615-21. PMID:15737203 doi:http://dx.doi.org/10.1111/j.0022-202X.2005.23623.x
- ↑ Tanaka S, Tamura M, Aoki A, Fujii T, Komiyama H, Sagai T, Shiroishi T. A new Gsdma3 mutation affecting anagen phase of first hair cycle. Biochem Biophys Res Commun. 2007 Aug 10;359(4):902-7. Epub 2007 Jun 8. PMID:17572385 doi:http://dx.doi.org/10.1016/j.bbrc.2007.05.209
- ↑ Runkel F, Marquardt A, Stoeger C, Kochmann E, Simon D, Kohnke B, Korthaus D, Wattler F, Fuchs H, Hrabe de Angelis M, Stumm G, Nehls M, Wattler S, Franz T, Augustin M. The dominant alopecia phenotypes Bareskin, Rex-denuded, and Reduced Coat 2 are caused by mutations in gasdermin 3. Genomics. 2004 Nov;84(5):824-35. PMID:15475261 doi:http://dx.doi.org/S0888-7543(04)00179-X
- ↑ Shi J, Zhao Y, Wang K, Shi X, Wang Y, Huang H, Zhuang Y, Cai T, Wang F, Shao F. Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death. Nature. 2015 Oct 29;526(7575):660-5. doi: 10.1038/nature15514. Epub 2015 Sep 16. PMID:26375003 doi:http://dx.doi.org/10.1038/nature15514
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