View source for 9uxv


==Crystal structure of GSDME==
<StructureSection load='9uxv' size='340' side='right'caption='[[9uxv]], [[Resolution|resolution]] 2.95&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9uxv]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Danio_rerio Danio rerio], [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9UXV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9UXV FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.95&#8491;</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=9uxv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9uxv OCA], [https://pdbe.org/9uxv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9uxv RCSB], [https://www.ebi.ac.uk/pdbsum/9uxv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9uxv ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/GSDME_HUMAN GSDME_HUMAN] Rare autosomal dominant non-syndromic sensorineural deafness type DFNA. The disease is caused by variants affecting the gene represented in this entry.  Is a tumor suppressor gene with an important role in colorectal cancer (CRC).<ref>PMID:18223688</ref> 
== Function ==
[https://www.uniprot.org/uniprot/Q6J2R6_DANRE Q6J2R6_DANRE] [https://www.uniprot.org/uniprot/GSDME_HUMAN GSDME_HUMAN] Precursor of a pore-forming protein that converts non-inflammatory apoptosis to pyroptosis (PubMed:27281216, PubMed:28459430, PubMed:33852854, PubMed:35594856, PubMed:36607699). This form constitutes the precursor of the pore-forming protein: upon cleavage, the released N-terminal moiety (Gasdermin-E, N-terminal) binds to membranes and forms pores, triggering pyroptosis (PubMed:28459430).<ref>PMID:27281216</ref> <ref>PMID:28459430</ref> <ref>PMID:33852854</ref> <ref>PMID:35594856</ref> <ref>PMID:36607699</ref>   Pore-forming protein produced by cleavage by CASP3 or granzyme B (GZMB), which converts non-inflammatory apoptosis to pyroptosis or promotes granzyme-mediated pyroptosis, respectively (PubMed:27281216, PubMed:28459430, PubMed:32188940, PubMed:33852854, PubMed:35594856). After cleavage, moves to the plasma membrane, homooligomerizes within the membrane and forms pores of 10-15 nanometers (nm) of inner diameter, allowing the release of mature interleukins (IL1B and IL16) and triggering pyroptosis (PubMed:28459430, PubMed:32188940, PubMed:33852854, PubMed:35594856). Binds to inner leaflet lipids, bisphosphorylated phosphatidylinositols, such as phosphatidylinositol (4,5)-bisphosphate (PubMed:28459430). Cleavage by CASP3 switches CASP3-mediated apoptosis induced by TNF or danger signals, such as chemotherapy drugs, to pyroptosis (PubMed:27281216, PubMed:28459430, PubMed:32188940). Mediates secondary necrosis downstream of the mitochondrial apoptotic pathway and CASP3 activation as well as in response to viral agents (PubMed:28045099). Exhibits bactericidal activity (PubMed:27281216). Cleavage by GZMB promotes tumor suppressor activity by triggering robust anti-tumor immunity (PubMed:21522185, PubMed:32188940). Suppresses tumors by mediating granzyme-mediated pyroptosis in target cells of natural killer (NK) cells: cleavage by granzyme B (GZMB), delivered to target cells from NK-cells, triggers pyroptosis of tumor cells and tumor suppression (PubMed:31953257, PubMed:32188940). May play a role in the p53/TP53-regulated cellular response to DNA damage (PubMed:16897187).<ref>PMID:16897187</ref> <ref>PMID:21522185</ref> <ref>PMID:27281216</ref> <ref>PMID:28045099</ref> <ref>PMID:28459430</ref> <ref>PMID:31953257</ref> <ref>PMID:32188940</ref> <ref>PMID:33852854</ref> <ref>PMID:35594856</ref>   (Microbial infection) Pore-forming protein, which promotes maternal placental pyroptosis in response to Zika virus infection, contributing to adverse fetal outcomes.<ref>PMID:35972780</ref> [https://www.uniprot.org/uniprot/GSDMD_MOUSE 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).<ref>PMID:26375003</ref> <ref>PMID:26375259</ref> <ref>PMID:26611636</ref> <ref>PMID:27383986</ref> <ref>PMID:27385778</ref> <ref>PMID:27418190</ref> 
== References ==
<references/>
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</StructureSection>
[[Category: Danio rerio]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Li S]]
[[Category: Liu Z]]
[[Category: Xiao TS]]