Gasdermin
From Proteopedia
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<StructureSection load='6cb8' size='340' side='right' caption='Cryo-EM mouse gasdermin A3 pore complex with cardiolipin (PDB code [[6cb8]])' scene=''> | <StructureSection load='6cb8' size='340' side='right' caption='Cryo-EM mouse gasdermin A3 pore complex with cardiolipin (PDB code [[6cb8]])' scene=''> | ||
| - | '''Gasdermin''' (GSDM) is the substrate of the inflamamatory [[Caspase]] downstream from inflamasomes which activate caspase. Inflammasomes are supramolecular signaling assemblies activating the lytic process against exogenous pathogens. GSDM is required for cytokine release and pyroptosis <ref>PMID:31451512</ref>. Pyropptosis is the regulated lytic cell death mediated by GSMD pore formation. GSDM D contains 2 domains: the N-terminal fragment which is pore-forming and the repressive C-terminal. The GSDM family contains 6 members in human. | ||
== Function == | == Function == | ||
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| + | '''Gasdermin''' (GSDM) is the substrate of the inflammatory [[Caspase]] downstream from inflammasomes which activate caspase. Inflammasomes are supramolecular signalling assemblies activating the lytic process against exogenous pathogens. GSDM is required for cytokine release and pyroptosis, a lytic form of programmed cell death) <ref>PMID:31451512</ref>. Pyropptosis is the regulated lytic cell death mediated by GSMD pore formation. GSDM D contains 2 domains: the N-terminal fragment which is pore-forming and the repressive C-terminal. The GSDM family contains 6 members in human. | ||
== Disease == | == Disease == | ||
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| + | GSDM is implicated in autoimmune diseases and certain cancers. | ||
== Relevance == | == Relevance == | ||
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| + | Because of its potential as a driver of inflammation in septic shock and autoimmune diseases GSMD D is an attractive drug target<ref>PMID:31548300</ref>, <ref>PMID:33692549</ref>. | ||
== Structural highlights == | == Structural highlights == | ||
Revision as of 09:57, 11 July 2022
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References
- ↑ Xia S, Hollingsworth LR 4th, Wu H. Mechanism and Regulation of Gasdermin-Mediated Cell Death. Cold Spring Harb Perspect Biol. 2020 Mar 2;12(3). pii: cshperspect.a036400. doi: , 10.1101/cshperspect.a036400. PMID:31451512 doi:http://dx.doi.org/10.1101/cshperspect.a036400
- ↑ Orning P, Lien E, Fitzgerald KA. Gasdermins and their role in immunity and inflammation. J Exp Med. 2019 Nov 4;216(11):2453-2465. doi: 10.1084/jem.20190545. Epub 2019 Sep, 23. PMID:31548300 doi:http://dx.doi.org/10.1084/jem.20190545
- ↑ Liu X, Xia S, Zhang Z, Wu H, Lieberman J. Channelling inflammation: gasdermins in physiology and disease. Nat Rev Drug Discov. 2021 May;20(5):384-405. doi: 10.1038/s41573-021-00154-z., Epub 2021 Mar 10. PMID:33692549 doi:http://dx.doi.org/10.1038/s41573-021-00154-z
