5h8o

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Current revision (07:27, 9 August 2023) (edit) (undo)
 
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<StructureSection load='5h8o' size='340' side='right'caption='[[5h8o]], [[Resolution|resolution]] 4.21&Aring;' scene=''>
<StructureSection load='5h8o' size='340' side='right'caption='[[5h8o]], [[Resolution|resolution]] 4.21&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[5h8o]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Camelus_glama Camelus glama] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5H8O OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5H8O FirstGlance]. <br>
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<table><tr><td colspan='2'>[[5h8o]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Lama_glama Lama glama]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5H8O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5H8O FirstGlance]. <br>
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</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5h8d|5h8d]]</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]] 4.206&#8491;</td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PYCARD, ASC, CARD5, TMS1 ([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=5h8o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5h8o OCA], [https://pdbe.org/5h8o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5h8o RCSB], [https://www.ebi.ac.uk/pdbsum/5h8o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5h8o ProSAT]</span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5h8o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5h8o OCA], [http://pdbe.org/5h8o PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5h8o RCSB], [http://www.ebi.ac.uk/pdbsum/5h8o PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5h8o ProSAT]</span></td></tr>
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</table>
</table>
== Function ==
== Function ==
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[[http://www.uniprot.org/uniprot/ASC_HUMAN ASC_HUMAN]] Functions as key mediator in apoptosis and inflammation. Promotes caspase-mediated apoptosis involving predominantly caspase-8 and also caspase-9 in a probable cell type-specific manner. Involved in activation of the mitochondrial apoptotic pathway, promotes caspase-8-dependent proteolytic maturation of BID independently of FADD in certain cell types and also mediates mitochondrial translocation of BAX and activates BAX-dependent apoptosis coupled to activation of caspase-9, -2 and -3. Involved in macrophage pyroptosis, a caspase-1-dependent inflammatory form of cell death and is the major constituent of the ASC pyroptosome which forms upon potassium depletion and rapidly recruits and activates caspase-1. In innate immune response believed to act as an integral adapter in the assembly of the inflammasome which activates caspase-1 leading to processing and secretion of proinflammatory cytokines. The function as activating adapter in different types of inflammasomes is mediated by the DAPIN and CARD domains and their homotypic interactions. Required for recruitment of caspase-1 to inflammasomes containing certain pattern recognition receptors, such as NLRP2, NLRP3, AIM2 and probably IFI16. In the NLRP1 and NLRC4 inflammasomes seems not be required but facilitates the processing of procaspase-1. In cooperation with NOD2 involved in an inflammasome activated by bacterial muramyl dipeptide leading to caspase-1 activation. May be involved in DDX58-triggered proinflammatory responses and inflammasome activation. Isoform 2 may have a regulating effect on the function as inflammasome adapter. Isoform 3 seems to inhibit inflammasome-mediated maturation of interleukin-1 beta. In collaboration with AIM2 which detects cytosolic double-stranded DNA may also be involved in a caspase-1-independent cell death that involves caspase-8. In adaptive immunity may be involved in maturation of dendritic cells to stimulate T-cell immunity and in cytoskeletal rearrangements coupled to chemotaxis and antigen uptake may be involved in post-transcriptional regulation of the guanine nucleotide exchange factor DOCK2; the latter function is proposed to involve the nuclear form. Also involved in transcriptional activation of cytokines and chemokines independent of the inflammasome; this function may involve AP-1, NF-kappa-B, MAPK and caspase-8 signaling pathways. For regulation of NF-kappa-B activating and inhibiting functions have been reported. Modulates NF-kappa-B induction at the level of the IKK complex by inhibiting kinase activity of CHUK and IKBK. Proposed to compete with RIPK2 for association with CASP1 thereby down-regulating CASP1-mediated RIPK2-dependent NF-kappa-B activation and activating interleukin-1 beta processing.<ref>PMID:19759850</ref> <ref>PMID:11103777</ref> <ref>PMID:12486103</ref> <ref>PMID:12646168</ref> <ref>PMID:15030775</ref> <ref>PMID:14730312</ref> <ref>PMID:16585594</ref> <ref>PMID:16982856</ref> <ref>PMID:17599095</ref> <ref>PMID:17349957</ref> <ref>PMID:16964285</ref> <ref>PMID:19234215</ref> <ref>PMID:19494289</ref> <ref>PMID:19158676</ref> <ref>PMID:19158675</ref> <ref>PMID:20482797</ref> <ref>PMID:21487011</ref> <ref>PMID:22732093</ref> <ref>PMID:14499617</ref>
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[https://www.uniprot.org/uniprot/ASC_HUMAN ASC_HUMAN] Functions as key mediator in apoptosis and inflammation. Promotes caspase-mediated apoptosis involving predominantly caspase-8 and also caspase-9 in a probable cell type-specific manner. Involved in activation of the mitochondrial apoptotic pathway, promotes caspase-8-dependent proteolytic maturation of BID independently of FADD in certain cell types and also mediates mitochondrial translocation of BAX and activates BAX-dependent apoptosis coupled to activation of caspase-9, -2 and -3. Involved in macrophage pyroptosis, a caspase-1-dependent inflammatory form of cell death and is the major constituent of the ASC pyroptosome which forms upon potassium depletion and rapidly recruits and activates caspase-1. In innate immune response believed to act as an integral adapter in the assembly of the inflammasome which activates caspase-1 leading to processing and secretion of proinflammatory cytokines. The function as activating adapter in different types of inflammasomes is mediated by the DAPIN and CARD domains and their homotypic interactions. Required for recruitment of caspase-1 to inflammasomes containing certain pattern recognition receptors, such as NLRP2, NLRP3, AIM2 and probably IFI16. In the NLRP1 and NLRC4 inflammasomes seems not be required but facilitates the processing of procaspase-1. In cooperation with NOD2 involved in an inflammasome activated by bacterial muramyl dipeptide leading to caspase-1 activation. May be involved in DDX58-triggered proinflammatory responses and inflammasome activation. Isoform 2 may have a regulating effect on the function as inflammasome adapter. Isoform 3 seems to inhibit inflammasome-mediated maturation of interleukin-1 beta. In collaboration with AIM2 which detects cytosolic double-stranded DNA may also be involved in a caspase-1-independent cell death that involves caspase-8. In adaptive immunity may be involved in maturation of dendritic cells to stimulate T-cell immunity and in cytoskeletal rearrangements coupled to chemotaxis and antigen uptake may be involved in post-transcriptional regulation of the guanine nucleotide exchange factor DOCK2; the latter function is proposed to involve the nuclear form. Also involved in transcriptional activation of cytokines and chemokines independent of the inflammasome; this function may involve AP-1, NF-kappa-B, MAPK and caspase-8 signaling pathways. For regulation of NF-kappa-B activating and inhibiting functions have been reported. Modulates NF-kappa-B induction at the level of the IKK complex by inhibiting kinase activity of CHUK and IKBK. Proposed to compete with RIPK2 for association with CASP1 thereby down-regulating CASP1-mediated RIPK2-dependent NF-kappa-B activation and activating interleukin-1 beta processing.<ref>PMID:19759850</ref> <ref>PMID:11103777</ref> <ref>PMID:12486103</ref> <ref>PMID:12646168</ref> <ref>PMID:15030775</ref> <ref>PMID:14730312</ref> <ref>PMID:16585594</ref> <ref>PMID:16982856</ref> <ref>PMID:17599095</ref> <ref>PMID:17349957</ref> <ref>PMID:16964285</ref> <ref>PMID:19234215</ref> <ref>PMID:19494289</ref> <ref>PMID:19158676</ref> <ref>PMID:19158675</ref> <ref>PMID:20482797</ref> <ref>PMID:21487011</ref> <ref>PMID:22732093</ref> <ref>PMID:14499617</ref>
<div style="background-color:#fffaf0;">
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
== Publication Abstract from PubMed ==
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==See Also==
==See Also==
*[[Antibody 3D structures|Antibody 3D structures]]
*[[Antibody 3D structures|Antibody 3D structures]]
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*[[3D structures of non-human antibody|3D structures of non-human antibody]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Camelus glama]]
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[[Category: Homo sapiens]]
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[[Category: Human]]
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[[Category: Lama glama]]
[[Category: Large Structures]]
[[Category: Large Structures]]
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[[Category: Lu, A]]
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[[Category: Lu A]]
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[[Category: Ploegh, H L]]
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[[Category: Ploegh HL]]
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[[Category: Ruan, J]]
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[[Category: Ruan J]]
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[[Category: Schmidt, F I]]
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[[Category: Schmidt FI]]
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[[Category: Tang, C]]
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[[Category: Tang C]]
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[[Category: Wu, H]]
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[[Category: Wu H]]
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[[Category: Antibody fragment]]
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[[Category: Asc-binding]]
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[[Category: Immune system]]
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[[Category: Inflammasome]]
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[[Category: Vhh nanobody]]
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Current revision

Crystal structure of an ASC-binding nanobody in complex with the CARD domain of ASC

PDB ID 5h8o

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