This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.

6ao3

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Revision as of 17:39, 11 December 2019

Crystal structure of the murine gasdermin D C-terminal domain

Structural highlights

6ao3 is a 4 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.
Gene:	Gsdmdc1, Gsdmd (LK3 transgenic mice)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[GSDMD_MOUSE] Gasdermin-D, N-terminal: Promotes pyroptosis in response to microbial infection and danger signals. Produced by the cleavage of gasdermin-D by inflammatory caspases CASP1 or CASP4 in response to canonical, as well as non-canonical (such as cytosolic LPS) inflammasome activators (PubMed:26611636, PubMed:26375259, PubMed:26375003, PubMed:27418190, PubMed:27385778, PubMed:27383986). After cleavage, moves to the plasma membrane where it strongly binds to membrane inner leaflet lipids, including monophosphorylated phosphatidylinositols, such as phosphatidylinositol 4-phosphate, bisphosphorylated phosphatidylinositols, such as phosphatidylinositol (4,5)-bisphosphate, as well as phosphatidylinositol (3,4,5)-trisphosphate, and more weakly to phosphatidic acid and phosphatidylserine. Homooligomerizes within the membrane and forms pores of 10 - 15 nanometers (nm) of inner diameter, allowing the release of mature IL1B and triggering pyroptosis. Exhibits bactericidal activity. Gasdermin-D, N-terminal released from pyroptotic cells into the extracellular milieu rapidly binds to and kills both Gram-negative and Gram-positive bacteria, without harming neighboring mammalian cells, as it does not disrupt the plasma membrane from the outside due to lipid-binding specificity. Under cell culture conditions, also active against intracellular bacteria, such as Listeria monocytogenes. Strongly binds to bacterial and mitochondrial lipids, including cardiolipin. Does not bind to phosphatidylethanolamine or phosphatidylcholine (PubMed:27383986).^[1] ^[2] ^[3] ^[4] ^[5] ^[6]

Publication Abstract from PubMed

Pyroptosis is an inflammatory form of programmed cell death that plays important roles in immune protection against infections and in inflammatory disorders. Gasdermin D (GSDMD) is an executor of pyroptosis upon cleavage by caspases-1/4/5/11 following canonical and noncanonical inflammasome activation. GSDMD N-terminal domain assembles membrane pores to induce cytolysis, whereas its C-terminal domain inhibits cell death through intramolecular association with the N domain. The molecular mechanisms of autoinhibition for GSDMD are poorly characterized. Here we report the crystal structures of the human and murine GSDMD C-terminal domains, which differ from those of the full-length murine GSDMA3 and the human GSDMB C-terminal domain. Mutations of GSDMD C-domain residues predicted to locate at its interface with the N-domain enhanced pyroptosis. Our results suggest that GSDMDs may employ a distinct mode of intramolecular domain interaction and autoinhibition, which may be relevant to its unique role in pyroptosis downstream of inflammasome activation.

Structures of the Gasdermin D C-Terminal Domains Reveal Mechanisms of Autoinhibition.,Liu Z, Wang C, Rathkey JK, Yang J, Dubyak GR, Abbott DW, Xiao TS Structure. 2018 Mar 14. pii: S0969-2126(18)30082-0. doi:, 10.1016/j.str.2018.03.002. PMID:29576317^[7]

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

References

↑ 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
↑ Kayagaki N, Stowe IB, Lee BL, O'Rourke K, Anderson K, Warming S, Cuellar T, Haley B, Roose-Girma M, Phung QT, Liu PS, Lill JR, Li H, Wu J, Kummerfeld S, Zhang J, Lee WP, Snipas SJ, Salvesen GS, Morris LX, Fitzgerald L, Zhang Y, Bertram EM, Goodnow CC, Dixit VM. Caspase-11 cleaves gasdermin D for non-canonical inflammasome signalling. Nature. 2015 Oct 29;526(7575):666-71. doi: 10.1038/nature15541. Epub 2015 Sep 16. PMID:26375259 doi:http://dx.doi.org/10.1038/nature15541
↑ He WT, Wan H, Hu L, Chen P, Wang X, Huang Z, Yang ZH, Zhong CQ, Han J. Gasdermin D is an executor of pyroptosis and required for interleukin-1beta secretion. Cell Res. 2015 Dec;25(12):1285-98. doi: 10.1038/cr.2015.139. Epub 2015 Nov 27. PMID:26611636 doi:http://dx.doi.org/10.1038/cr.2015.139
↑ Liu X, Zhang Z, Ruan J, Pan Y, Magupalli VG, Wu H, Lieberman J. Inflammasome-activated gasdermin D causes pyroptosis by forming membrane pores. Nature. 2016 Jul 7;535(7610):153-8. doi: 10.1038/nature18629. PMID:27383986 doi:http://dx.doi.org/10.1038/nature18629
↑ Russo HM, Rathkey J, Boyd-Tressler A, Katsnelson MA, Abbott DW, Dubyak GR. Active Caspase-1 Induces Plasma Membrane Pores That Precede Pyroptotic Lysis and Are Blocked by Lanthanides. J Immunol. 2016 Aug 15;197(4):1353-67. doi: 10.4049/jimmunol.1600699. Epub 2016, Jul 6. PMID:27385778 doi:http://dx.doi.org/10.4049/jimmunol.1600699
↑ Sborgi L, Ruhl S, Mulvihill E, Pipercevic J, Heilig R, Stahlberg H, Farady CJ, Muller DJ, Broz P, Hiller S. GSDMD membrane pore formation constitutes the mechanism of pyroptotic cell death. EMBO J. 2016 Aug 15;35(16):1766-78. doi: 10.15252/embj.201694696. Epub 2016 Jul, 14. PMID:27418190 doi:http://dx.doi.org/10.15252/embj.201694696
↑ Liu Z, Wang C, Rathkey JK, Yang J, Dubyak GR, Abbott DW, Xiao TS. Structures of the Gasdermin D C-Terminal Domains Reveal Mechanisms of Autoinhibition. Structure. 2018 Mar 14. pii: S0969-2126(18)30082-0. doi:, 10.1016/j.str.2018.03.002. PMID:29576317 doi:http://dx.doi.org/10.1016/j.str.2018.03.002

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6ao3"

@@ Line 1: / Line 1: @@
 ==Crystal structure of the murine gasdermin D C-terminal domain==
-<StructureSection load='6ao3' size='340' side='right' caption='[[6ao3]], [[Resolution|resolution]] 1.76&Aring;' scene=''>
+<StructureSection load='6ao3' size='340' side='right'caption='[[6ao3]], [[Resolution|resolution]] 1.76&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6ao3]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6AO3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6AO3 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6ao3]] is a 4 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=6AO3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6AO3 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=6ao3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ao3 OCA], [http://pdbe.org/6ao3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ao3 RCSB], [http://www.ebi.ac.uk/pdbsum/6ao3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ao3 ProSAT]</span></td></tr>
+</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Gsdmdc1, Gsdmd ([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=6ao3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ao3 OCA], [http://pdbe.org/6ao3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ao3 RCSB], [http://www.ebi.ac.uk/pdbsum/6ao3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ao3 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 21: / Line 22: @@
 __TOC__
 </StructureSection>
+[[Category: Large Structures]]
+[[Category: Lk3 transgenic mice]]
 [[Category: Liu, Z]]
 [[Category: Wang, C]]

6ao3

From Proteopedia

Revision as of 17:39, 11 December 2019

Crystal structure of the murine gasdermin D C-terminal domain

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox