View source for 8et2


==CryoEM structure of the GSDMB pore==
<StructureSection load='8et2' size='340' side='right'caption='[[8et2]], [[Resolution|resolution]] 4.96&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8et2]] is a 24 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8ET2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8ET2 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 4.96&#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=8et2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8et2 OCA], [https://pdbe.org/8et2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8et2 RCSB], [https://www.ebi.ac.uk/pdbsum/8et2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8et2 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/GSDMB_HUMAN GSDMB_HUMAN] Precursor of a pore-forming protein that acts as a downstream mediator of granzyme-mediated cell death (PubMed:32299851). This form constitutes the precursor of the pore-forming protein: upon cleavage, the released N-terminal moiety (Gasdermin-B, N-terminal) binds to membranes and forms pores, triggering pyroptosis (PubMed:32299851). Also acts as a regulator of epithelial cell repair independently of programmed cell death: translocates to the plasma membrane and promotes epithelial maintenance and repair by regulating PTK2/FAK-mediated phosphorylation of PDGFA (PubMed:35021065).<ref>PMID:32299851</ref> <ref>PMID:35021065</ref>   Pore-forming protein produced by cleavage by granzyme A (GZMA), which causes membrane permeabilization and pyroptosis in target cells of cytotoxic T and natural killer (NK) cells (PubMed:27281216, PubMed:32299851). Key downstream mediator of granzyme-mediated cell death: (1) granzyme A (GZMA), delivered to target cells from cytotoxic T- and NK-cells, (2) specifically cleaves Gasdermin-B to generate this form (PubMed:32299851). After cleavage, moves to the plasma membrane, homooligomerizes within the membrane and forms pores of 10-15 nanometers (nm) of inner diameter, triggering pyroptosis (PubMed:32299851, PubMed:36599845, PubMed:36991122, PubMed:36991125). The different isoforms recognize and bind different phospholipids on membranes, promoting cell death of different target cells (PubMed:34022140, PubMed:36157507, PubMed:36991122, PubMed:36991125).<ref>PMID:27281216</ref> <ref>PMID:32299851</ref> <ref>PMID:34022140</ref> <ref>PMID:36157507</ref> <ref>PMID:36599845</ref> <ref>PMID:36991122</ref> <ref>PMID:36991125</ref>   Precursor of a pore-forming protein that acts as a downstream mediator of granzyme-mediated cell death and mediates pyroptosis (PubMed:28154144, PubMed:36157507, PubMed:36899106, PubMed:36991122, PubMed:36991125). Following cleavage and activation by granzyme A (GZMA), the N-terminal part binds to membrane inner leaflet lipids, homooligomerizes within the human plasma membrane and forms pores of 10-15 nanometers (nm) of inner diameter, triggering pyroptosis (PubMed:28154144, PubMed:36157507, PubMed:36899106, PubMed:36991122, PubMed:36991125). Recognizes and binds membrane inner leaflet lipids of human cells, such as phosphatidylinositol 4-phosphate, phosphatidylinositol 5-phosphate, bisphosphorylated phosphatidylinositols, such as phosphatidylinositol (4,5)-bisphosphate, and more weakly to phosphatidic acid (PubMed:28154144, PubMed:36157507). Also binds sufatide, a component of the apical membrane of epithelial cells (PubMed:28154144).<ref>PMID:28154144</ref> <ref>PMID:36157507</ref> <ref>PMID:36899106</ref> <ref>PMID:36991122</ref> <ref>PMID:36991125</ref>   Precursor of a pore-forming protein that acts as a downstream mediator of granzyme-mediated cell death and mediates pyroptosis of human cells (PubMed:36899106, PubMed:36991122, PubMed:36991125). Following cleavage and activation by granzyme A (GZMA), the N-terminal part binds to membrane inner leaflet lipids, homooligomerizes within the human plasma membrane and forms pores of 10-15 nanometers (nm) of inner diameter, triggering pyroptosis (PubMed:36899106, PubMed:36991122, PubMed:36991125).<ref>PMID:36899106</ref> <ref>PMID:36991122</ref> <ref>PMID:36991125</ref>   Precursor of a pore-forming protein that acts as a downstream mediator of granzyme-mediated cell death and specifically mediates cell death of Gram-negative bacteria in response to infection (PubMed:34022140). Following cleavage and activation by granzyme A (GZMA), the N-terminal part recognizes and binds phospholipids found on Gram-negative bacterial membranes, such as lipid A and cariolipin, homooligomerizes within the bacterial membranes and forms pores, triggering pyroptosis followed by cell death (PubMed:34022140). In contrast to isoform 4, does not bind to membrane inner leaflet lipids of host human cell, such as phosphatidylinositol 4-phosphate, phosphatidylinositol 5-phosphate, bisphosphorylated phosphatidylinositols, such as phosphatidylinositol (4,5)-bisphosphate (PubMed:34022140).<ref>PMID:34022140</ref>   Not able to trigger pyroptosis.<ref>PMID:36899106</ref> <ref>PMID:36991122</ref> <ref>PMID:36991125</ref>   Not able to trigger pyroptosis.<ref>PMID:36899106</ref> <ref>PMID:36991122</ref> <ref>PMID:36991125</ref> 
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Ruan J]]
[[Category: Wang C]]