5b5r

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Revision as of 12:22, 6 November 2017

Crystal structure of GSDMA3

Structural highlights

5b5r is a 1 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.
NonStd Res:
Gene:	Gsdma3, Gsdm3 (LK3 transgenic mice)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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]

Publication Abstract from PubMed

Inflammatory caspases cleave the gasdermin D (GSDMD) protein to trigger pyroptosis, a lytic form of cell death that is crucial for immune defences and diseases. GSDMD contains a functionally important gasdermin-N domain that is shared in the gasdermin family. The functional mechanism of action of gasdermin proteins is unknown. Here we show that the gasdermin-N domains of the gasdermin proteins GSDMD, GSDMA3 and GSDMA can bind membrane lipids, phosphoinositides and cardiolipin, and exhibit membrane-disrupting cytotoxicity in mammalian cells and artificially transformed bacteria. Gasdermin-N moved to the plasma membrane during pyroptosis. Purified gasdermin-N efficiently lysed phosphoinositide/cardiolipin-containing liposomes and formed pores on membranes made of artificial or natural phospholipid mixtures. Most gasdermin pores had an inner diameter of 10-14 nm and contained 16 symmetric protomers. The crystal structure of GSDMA3 showed an autoinhibited two-domain architecture that is conserved in the gasdermin family. Structure-guided mutagenesis demonstrated that the liposome-leakage and pore-forming activities of the gasdermin-N domain are required for pyroptosis. These findings reveal the mechanism for pyroptosis and provide insights into the roles of the gasdermin family in necrosis, immunity and diseases.

Pore-forming activity and structural autoinhibition of the gasdermin family.,Ding J, Wang K, Liu W, She Y, Sun Q, Shi J, Sun H, Wang DC, Shao F Nature. 2016 Jul 7;535(7610):111-6. PMID:27281216^[6]

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

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
↑ Ding J, Wang K, Liu W, She Y, Sun Q, Shi J, Sun H, Wang DC, Shao F. Pore-forming activity and structural autoinhibition of the gasdermin family. Nature. 2016 Jul 7;535(7610):111-6. PMID:27281216 doi:http://dx.doi.org/10.1038/nature18590

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5b5r"

Categories: Lk3 transgenic mice | Ding, J | Shao, F | Pyroptosis excutioner | Transport protein

@@ Line 3: / Line 3: @@
 <StructureSection load='5b5r' size='340' side='right' caption='[[5b5r]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5b5r]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5B5R OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5B5R FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5b5r]] 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=5B5R OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5B5R FirstGlance]. <br>
 </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></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='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=5b5r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5b5r OCA], [http://pdbe.org/5b5r PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5b5r RCSB], [http://www.ebi.ac.uk/pdbsum/5b5r PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5b5r ProSAT]</span></td></tr>
 </table>
@@ Line 24: / Line 25: @@
 __TOC__
 </StructureSection>
+[[Category: Lk3 transgenic mice]]
 [[Category: Ding, J]]
 [[Category: Shao, F]]
 [[Category: Pyroptosis excutioner]]
 [[Category: Transport protein]]

5b5r

From Proteopedia

Revision as of 12:22, 6 November 2017

Crystal structure of GSDMA3

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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