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-基本情報
登録情報 | データベース: PDB / ID: 7keu | ||||||
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タイトル | Cryo-EM structure of the Caspase-1-CARD:ASC-CARD octamer | ||||||
要素 |
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キーワード | IMMUNE SYSTEM (免疫系) / ASC / Apoptosis-associated speck-like protein containing a CARD / PYCARD / caspase-1 (カスパーゼ-1) / cryo-EM (低温電子顕微鏡法) / helical filament / octamer (オリゴマー) | ||||||
機能・相同性 | 機能・相同性情報 Pyrin domain binding / NLRP6 inflammasome complex / myosin I binding / positive regulation of antigen processing and presentation of peptide antigen via MHC class II / myeloid dendritic cell activation involved in immune response / regulation of intrinsic apoptotic signaling pathway / カスパーゼ-1 / protease inhibitor complex / myeloid dendritic cell activation / IkappaB kinase complex ...Pyrin domain binding / NLRP6 inflammasome complex / myosin I binding / positive regulation of antigen processing and presentation of peptide antigen via MHC class II / myeloid dendritic cell activation involved in immune response / regulation of intrinsic apoptotic signaling pathway / カスパーゼ-1 / protease inhibitor complex / myeloid dendritic cell activation / IkappaB kinase complex / AIM2 inflammasome complex assembly / The AIM2 inflammasome / AIM2 inflammasome complex / 飲作用 / IPAF inflammasome complex / The IPAF inflammasome / NLRP1 inflammasome complex / icosanoid biosynthetic process / interleukin-6 receptor binding / cytokine precursor processing / NLRP3 inflammasome complex assembly / canonical inflammasome complex / positive regulation of adaptive immune response / positive regulation of interleukin-18 production / BMP receptor binding / NLRP3 inflammasome complex / caspase binding / CARD domain binding / osmosensory signaling pathway / negative regulation of protein serine/threonine kinase activity / negative regulation of interferon-beta production / CLEC7A/inflammasome pathway / positive regulation of cysteine-type endopeptidase activity / regulation of tumor necrosis factor-mediated signaling pathway / positive regulation of tumor necrosis factor-mediated signaling pathway / Interleukin-1 processing / Interleukin-37 signaling / positive regulation of extrinsic apoptotic signaling pathway / positive regulation of macrophage cytokine production / pattern recognition receptor signaling pathway / cellular response to organic substance / positive regulation of actin filament polymerization / tropomyosin binding / negative regulation of NF-kappaB transcription factor activity / positive regulation of activated T cell proliferation / signaling receptor ligand precursor processing / TP53 Regulates Transcription of Caspase Activators and Caspases / pyroptotic inflammatory response / cysteine-type endopeptidase activator activity involved in apoptotic process / positive regulation of release of cytochrome c from mitochondria / positive regulation of interleukin-10 production / positive regulation of cysteine-type endopeptidase activity involved in apoptotic process / protein autoprocessing / The NLRP3 inflammasome / protein maturation / intrinsic apoptotic signaling pathway by p53 class mediator / negative regulation of cytokine production involved in inflammatory response / intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / positive regulation of T cell migration / Pyroptosis / cellular response to interleukin-1 / Purinergic signaling in leishmaniasis infection / positive regulation of phagocytosis / negative regulation of canonical NF-kappaB signal transduction / positive regulation of chemokine production / positive regulation of defense response to virus by host / tumor necrosis factor-mediated signaling pathway / activation of innate immune response / positive regulation of interleukin-1 beta production / regulation of autophagy / positive regulation of interleukin-8 production / positive regulation of JNK cascade / regulation of protein stability / NOD1/2 Signaling Pathway / protein homooligomerization / kinase binding / cellular response to type II interferon / positive regulation of inflammatory response / positive regulation of DNA-binding transcription factor activity / positive regulation of interleukin-6 production / cellular response to mechanical stimulus / positive regulation of non-canonical NF-kappaB signal transduction / activation of cysteine-type endopeptidase activity involved in apoptotic process / SARS-CoV-1 activates/modulates innate immune responses / azurophil granule lumen / positive regulation of T cell activation / positive regulation of type II interferon production / positive regulation of tumor necrosis factor production / positive regulation of NF-kappaB transcription factor activity / cellular response to tumor necrosis factor / regulation of inflammatory response / secretory granule lumen / positive regulation of canonical NF-kappaB signal transduction / defense response to virus / regulation of apoptotic process / endopeptidase activity / 微小管 / cellular response to lipopolysaccharide / protease binding / defense response to Gram-negative bacterium 類似検索 - 分子機能 | ||||||
生物種 | Homo sapiens (ヒト) | ||||||
手法 | 電子顕微鏡法 / 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.9 Å | ||||||
データ登録者 | Hollingsworth, L.R. / David, L. / Li, Y. / Ruan, J. / Wu, H. | ||||||
資金援助 | 米国, 1件
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引用 | ジャーナル: Nat Commun / 年: 2021 タイトル: Mechanism of filament formation in UPA-promoted CARD8 and NLRP1 inflammasomes. 著者: L Robert Hollingsworth / Liron David / Yang Li / Andrew R Griswold / Jianbin Ruan / Humayun Sharif / Pietro Fontana / Elizabeth L Orth-He / Tian-Min Fu / Daniel A Bachovchin / Hao Wu / 要旨: NLRP1 and CARD8 are related cytosolic sensors that upon activation form supramolecular signalling complexes known as canonical inflammasomes, resulting in caspase-1 activation, cytokine maturation ...NLRP1 and CARD8 are related cytosolic sensors that upon activation form supramolecular signalling complexes known as canonical inflammasomes, resulting in caspase-1 activation, cytokine maturation and/or pyroptotic cell death. NLRP1 and CARD8 use their C-terminal (CT) fragments containing a caspase recruitment domain (CARD) and the UPA (conserved in UNC5, PIDD, and ankyrins) subdomain for self-oligomerization, which in turn form the platform to recruit the inflammasome adaptor ASC (apoptosis-associated speck-like protein containing a CARD) or caspase-1, respectively. Here, we report cryo-EM structures of NLRP1-CT and CARD8-CT assemblies, in which the respective CARDs form central helical filaments that are promoted by oligomerized, but flexibly linked, UPAs surrounding the filaments. Through biochemical and cellular approaches, we demonstrate that the UPA itself reduces the threshold needed for NLRP1-CT and CARD8-CT filament formation and signalling. Structural analyses provide insights on the mode of ASC recruitment by NLRP1-CT and the contrasting direct recruitment of caspase-1 by CARD8-CT. We also discover that subunits in the central NLRP1 filament dimerize with additional exterior CARDs, which roughly doubles its thickness and is unique among all known CARD filaments. Finally, we engineer and determine the structure of an ASC-caspase-1 octamer, which suggests that ASC uses opposing surfaces for NLRP1, versus caspase-1, recruitment. Together these structures capture the architecture and specificity of the active NLRP1 and CARD8 inflammasomes in addition to key heteromeric CARD-CARD interactions governing inflammasome signalling. | ||||||
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-構造の表示
ムービー |
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構造ビューア | 分子: MolmilJmol/JSmol |
-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 7keu.cif.gz | 137.5 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb7keu.ent.gz | 105.9 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 7keu.json.gz | ツリー表示 | PDBx/mmJSON形式 | |
その他 | その他のダウンロード |
-検証レポート
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/ke/7keu ftp://data.pdbj.org/pub/pdb/validation_reports/ke/7keu | HTTPS FTP |
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-関連構造データ
関連構造データ | 22233MC 6xkjC 6xkkC M: このデータのモデリングに利用したマップデータ C: 同じ文献を引用 (文献) |
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類似構造データ | |
電子顕微鏡画像生データ | EMPIAR-10566 (タイトル: ASC-CARD:Caspase-1-CARD octamer / Data size: 1.2 TB Data #1: Unaligned multi-frame micrographs for the ASC-CASP1 CARD octamer [micrographs - multiframe]) |
-リンク
-集合体
登録構造単位 |
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非結晶学的対称性 (NCS) | NCSドメイン:
NCSドメイン領域: Component-ID: 0 / Refine code: 0
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