6kmz

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Current revision (10:37, 22 November 2023) (edit) (undo)
 
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<StructureSection load='6kmz' size='340' side='right'caption='[[6kmz]], [[Resolution|resolution]] 3.61&Aring;' scene=''>
<StructureSection load='6kmz' size='340' side='right'caption='[[6kmz]], [[Resolution|resolution]] 3.61&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[6kmz]] is a 10 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6KMZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6KMZ FirstGlance]. <br>
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<table><tr><td colspan='2'>[[6kmz]] is a 10 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=6KMZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6KMZ FirstGlance]. <br>
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</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6kmt|6kmt]]</td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.61&#8491;</td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CASP4, ICH2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), GSDMD, DFNA5L, GSDMDC1, FKSG10 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6kmz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6kmz OCA], [https://pdbe.org/6kmz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6kmz RCSB], [https://www.ebi.ac.uk/pdbsum/6kmz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6kmz ProSAT]</span></td></tr>
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<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Caspase-4 Caspase-4], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.57 3.4.22.57] </span></td></tr>
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<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=6kmz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6kmz OCA], [http://pdbe.org/6kmz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6kmz RCSB], [http://www.ebi.ac.uk/pdbsum/6kmz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6kmz ProSAT]</span></td></tr>
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</table>
</table>
== Function ==
== Function ==
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[[http://www.uniprot.org/uniprot/CASP4_HUMAN CASP4_HUMAN]] Inflammatory caspase (PubMed:7797510, PubMed:23516580, PubMed:25119034). Essential effector of NLRP3 inflammasome-dependent CASP1 activation and IL1B and IL18 secretion in response to non-canonical activators, such as UVB radiation, cholera enterotoxin subunit B and cytosolic LPS (PubMed:22246630, PubMed:26174085, PubMed:26173988, PubMed:26508369, PubMed:25964352). Independently of NLRP3 inflammasome and CASP1, promotes pyroptosis, through GSDMD cleavage and activation, and IL1A, IL18 and HMGB1 release in response to non-canonical inflammasome activators (PubMed:24879791, PubMed:25964352). Plays a crucial role in the restriction of Salmonella typhimurium replication in colonic epithelial cells during infection (PubMed:25121752). In later stages of the infection, LPS from cytosolic Salmonella triggers CASP4 activation, which ultimately results in pyroptosis of infected cells and their extrusion into the gut lumen, as well as in IL18 secretion. Pyroptosis limits bacterial replication, while cytokine secretion promotes the recruitment and activation of immune cells and triggers mucosal inflammation. Involved in LPS-induced IL6 secretion; this activity may not require caspase enzymatic activity (PubMed:26508369). Involved in cell death induced by endoplasmic reticulum stress and by treatment with cytotoxic APP peptides found Alzheimer's patient brains (PubMed:15123740, PubMed:22246630, PubMed:23661706). Activated by direct binding to LPS without the need of an upstream sensor (PubMed:25119034). Does not directly process IL1B (PubMed:7743998, PubMed:7797592, PubMed:7797510). During non-canonical inflammasome activation, cuts CGAS and may play a role in the regulation of antiviral innate immune activation (PubMed:28314590).<ref>PMID:15123740</ref> <ref>PMID:22246630</ref> <ref>PMID:23516580</ref> <ref>PMID:23661706</ref> <ref>PMID:24879791</ref> <ref>PMID:25119034</ref> <ref>PMID:25121752</ref> <ref>PMID:25964352</ref> <ref>PMID:26173988</ref> <ref>PMID:26174085</ref> <ref>PMID:26508369</ref> <ref>PMID:28314590</ref> <ref>PMID:7743998</ref> <ref>PMID:7797510</ref> <ref>PMID:7797592</ref> [[http://www.uniprot.org/uniprot/GSDMD_HUMAN GSDMD_HUMAN]] 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:26375003, PubMed:26375259, PubMed:27418190). After cleavage, moves to the plasma membrane where it strongly binds to 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)-bisphosphate, and more weakly to phosphatidic acid and phosphatidylserine (PubMed:27281216). Homooligomerizes within the membrane and forms pores of 10 - 15 nanometers (nm) of inner diameter, possibly allowing the release of mature IL1B and triggering pyroptosis (PubMed:27418190, PubMed:27281216). 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 (PubMed:27281216). Under cell culture conditions, also active against intracellular bacteria, such as Listeria monocytogenes (By similarity). Strongly binds to bacterial and mitochondrial lipids, including cardiolipin. Does not bind to unphosphorylated phosphatidylinositol, phosphatidylethanolamine nor phosphatidylcholine (PubMed:27281216).[UniProtKB:Q9D8T2]<ref>PMID:26375003</ref> <ref>PMID:26375259</ref> <ref>PMID:27281216</ref> <ref>PMID:27418190</ref>
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[https://www.uniprot.org/uniprot/CASP4_HUMAN CASP4_HUMAN] Inflammatory caspase (PubMed:7797510, PubMed:23516580, PubMed:25119034). Essential effector of NLRP3 inflammasome-dependent CASP1 activation and IL1B and IL18 secretion in response to non-canonical activators, such as UVB radiation, cholera enterotoxin subunit B and cytosolic LPS (PubMed:22246630, PubMed:26174085, PubMed:26173988, PubMed:26508369, PubMed:25964352). Independently of NLRP3 inflammasome and CASP1, promotes pyroptosis, through GSDMD cleavage and activation, and IL1A, IL18 and HMGB1 release in response to non-canonical inflammasome activators (PubMed:24879791, PubMed:25964352). Plays a crucial role in the restriction of Salmonella typhimurium replication in colonic epithelial cells during infection (PubMed:25121752). In later stages of the infection, LPS from cytosolic Salmonella triggers CASP4 activation, which ultimately results in pyroptosis of infected cells and their extrusion into the gut lumen, as well as in IL18 secretion. Pyroptosis limits bacterial replication, while cytokine secretion promotes the recruitment and activation of immune cells and triggers mucosal inflammation. Involved in LPS-induced IL6 secretion; this activity may not require caspase enzymatic activity (PubMed:26508369). Involved in cell death induced by endoplasmic reticulum stress and by treatment with cytotoxic APP peptides found Alzheimer's patient brains (PubMed:15123740, PubMed:22246630, PubMed:23661706). Activated by direct binding to LPS without the need of an upstream sensor (PubMed:25119034). Does not directly process IL1B (PubMed:7743998, PubMed:7797592, PubMed:7797510). During non-canonical inflammasome activation, cuts CGAS and may play a role in the regulation of antiviral innate immune activation (PubMed:28314590).<ref>PMID:15123740</ref> <ref>PMID:22246630</ref> <ref>PMID:23516580</ref> <ref>PMID:23661706</ref> <ref>PMID:24879791</ref> <ref>PMID:25119034</ref> <ref>PMID:25121752</ref> <ref>PMID:25964352</ref> <ref>PMID:26173988</ref> <ref>PMID:26174085</ref> <ref>PMID:26508369</ref> <ref>PMID:28314590</ref> <ref>PMID:7743998</ref> <ref>PMID:7797510</ref> <ref>PMID:7797592</ref>
<div style="background-color:#fffaf0;">
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
== Publication Abstract from PubMed ==
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</div>
</div>
<div class="pdbe-citations 6kmz" style="background-color:#fffaf0;"></div>
<div class="pdbe-citations 6kmz" style="background-color:#fffaf0;"></div>
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==See Also==
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*[[Caspase 3D structures|Caspase 3D structures]]
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*[[Gasdermin 3D structures|Gasdermin 3D structures]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Caspase-4]]
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[[Category: Homo sapiens]]
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[[Category: Human]]
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[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Ding, J]]
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[[Category: Ding J]]
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[[Category: Sun, Q]]
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[[Category: Sun Q]]
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[[Category: Immune system]]
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[[Category: Pyroptosis]]
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Current revision

caspase-4 P22/P10 C258A in complex with human GSDMD-C domain

PDB ID 6kmz

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Proteopedia Page Contributors and Editors (what is this?)

OCA

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