Gasdermin: Difference between revisions
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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. | '''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. | ||
*'''Gasdermin B''' has a role in antibacterial defense, inflammatory pathologies and cancer<ref>PMID:37997534</ref>. | |||
*'''Gasdermin D''' is a pore-forming protein involved in cell death of macrophages<ref>PMID:32800355</ref>. | *'''Gasdermin D''' is a pore-forming protein involved in cell death of macrophages<ref>PMID:32800355</ref>. | ||
Latest revision as of 10:18, 25 June 2024
FunctionGasdermin (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) [1]. 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.
DiseaseGSDM is implicated in autoimmune diseases and certain cancers. RelevanceBecause of its potential as a driver of inflammation in septic shock and autoimmune diseases GSMD D is an attractive drug target[4], [5]. Structural highlightsThe 3D structure of GSDM A3 shows the monomer of the pore formed by the N-terminal of the molecule. Each subunit contributes 4 long β strands to the transmembrane region of the pore. The pore is formed by 27-fold symmetry[6]. 3D structures of gasdermin
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ReferencesReferences
- ↑ 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
- ↑ Sarrio D, Colomo S, Moreno-Bueno G. Gasdermin-B (GSDMB) takes center stage in antibacterial defense, inflammatory diseases, and cancer. FEBS J. 2023 Nov 23. PMID:37997534 doi:10.1111/febs.17018
- ↑ Xia S. Biological mechanisms and therapeutic relevance of the gasdermin family. Mol Aspects Med. 2020 Dec;76:100890. PMID:32800355 doi:10.1016/j.mam.2020.100890
- ↑ 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
- ↑ Ruan J, Xia S, Liu X, Lieberman J, Wu H. Cryo-EM structure of the gasdermin A3 membrane pore. Nature. 2018 May;557(7703):62-67. doi: 10.1038/s41586-018-0058-6. Epub 2018 Apr, 25. PMID:29695864 doi:http://dx.doi.org/10.1038/s41586-018-0058-6