+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 6xkk | ||||||
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タイトル | Cryo-EM structure of the NLRP1-CARD filament | ||||||
要素 | NACHT, LRR and PYD domains-containing protein 1 | ||||||
キーワード | IMMUNE SYSTEM (免疫系) / Filament / inflammasome (インフラマソーム) / signaling / UPA / CARD / FIIND / NLRP1 | ||||||
機能・相同性 | 機能・相同性情報 NLRP1 inflammasome complex assembly / cysteine-type endopeptidase activator activity / NLRP1 inflammasome complex / canonical inflammasome complex / The NLRP1 inflammasome / self proteolysis / 加水分解酵素; プロテアーゼ; ペプチド結合加水分解酵素 / stress-activated protein kinase signaling cascade / pattern recognition receptor activity / pattern recognition receptor signaling pathway ...NLRP1 inflammasome complex assembly / cysteine-type endopeptidase activator activity / NLRP1 inflammasome complex / canonical inflammasome complex / The NLRP1 inflammasome / self proteolysis / 加水分解酵素; プロテアーゼ; ペプチド結合加水分解酵素 / stress-activated protein kinase signaling cascade / pattern recognition receptor activity / pattern recognition receptor signaling pathway / cellular response to UV-B / pyroptotic inflammatory response / cysteine-type endopeptidase activator activity involved in apoptotic process / antiviral innate immune response / response to muramyl dipeptide / signaling adaptor activity / positive regulation of interleukin-1 beta production / molecular condensate scaffold activity / 加水分解酵素; 酸無水物に作用; 酸無水物に作用・細胞または細胞小器官の運動に関与 / protein homooligomerization / positive regulation of inflammatory response / activation of cysteine-type endopeptidase activity involved in apoptotic process / : / double-stranded RNA binding / peptidase activity / regulation of inflammatory response / double-stranded DNA binding / regulation of apoptotic process / neuron apoptotic process / defense response to virus / defense response to bacterium / protein domain specific binding / apoptotic process / 核小体 / enzyme binding / ATP hydrolysis activity / 核質 / ATP binding / 細胞核 / 細胞質基質 / 細胞質 類似検索 - 分子機能 | ||||||
生物種 | Homo sapiens (ヒト) | ||||||
手法 | 電子顕微鏡法 / らせん対称体再構成法 / クライオ電子顕微鏡法 / 解像度: 3.72 Å | ||||||
データ登録者 | Hollingsworth, L.R. / David, L. / Li, Y. / Sharif, H. / Fontana, P. / Fu, T. / 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 |
ムービービューア |
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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 | 6xkk.cif.gz | 676.7 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb6xkk.ent.gz | 527.4 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 6xkk.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/xk/6xkk ftp://data.pdbj.org/pub/pdb/validation_reports/xk/6xkk | HTTPS FTP |
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-関連構造データ
関連構造データ | 22220MC 6xkjC 7keuC 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-10564 (タイトル: NLRP1-CT filament / Data size: 534.7 Data #1: Unaligned multi-frame micrographs [micrographs - multiframe]) |
-リンク
-集合体
登録構造単位 |
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対称性 | らせん対称: (回転対称性: 1 / Dyad axis: no / N subunits divisor: 1 / Num. of operations: 44 / Rise per n subunits: 5.1 Å / Rotation per n subunits: -100.8 °) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
非結晶学的対称性 (NCS) | NCSドメイン:
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