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基本情報
登録情報 | データベース: PDB / ID: 8spb | |||||||||
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タイトル | Caspase-4/Pro-IL-18 complex | |||||||||
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![]() | IMMUNE SYSTEM / Innate immune / Complex | |||||||||
機能・相同性 | ![]() caspase-4 / non-canonical inflammasome complex / positive regulation of interleukin-18-mediated signaling pathway / interleukin-18 receptor binding / non-canonical inflammasome complex assembly / Interleukin-18 signaling / positive regulation of tissue remodeling / AIM2 inflammasome complex / IPAF inflammasome complex / NLRP1 inflammasome complex ...caspase-4 / non-canonical inflammasome complex / positive regulation of interleukin-18-mediated signaling pathway / interleukin-18 receptor binding / non-canonical inflammasome complex assembly / Interleukin-18 signaling / positive regulation of tissue remodeling / AIM2 inflammasome complex / IPAF inflammasome complex / NLRP1 inflammasome complex / positive regulation of T-helper 2 cell differentiation / positive regulation of T-helper 1 cell cytokine production / NLRP3 inflammasome complex / positive regulation of macrophage derived foam cell differentiation / CARD domain binding / caspase binding / positive regulation of interleukin-13 production / positive regulation of neuroinflammatory response / interleukin-18-mediated signaling pathway / natural killer cell mediated cytotoxicity / negative regulation of myoblast differentiation / type 2 immune response / natural killer cell activation / sleep / neutrophil activation / positive regulation of tumor necrosis factor-mediated signaling pathway / Interleukin-1 processing / positive regulation of NK T cell proliferation / triglyceride homeostasis / positive regulation of natural killer cell proliferation / positive regulation of granulocyte macrophage colony-stimulating factor production / T-helper 1 type immune response / positive regulation of activated T cell proliferation / pyroptotic inflammatory response / positive regulation of interleukin-17 production / Interleukin-10 signaling / protein autoprocessing / protein maturation / intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress / establishment of skin barrier / Pyroptosis / regulation of cell adhesion / Purinergic signaling in leishmaniasis infection / positive regulation of chemokine production / positive regulation of tyrosine phosphorylation of STAT protein / intrinsic apoptotic signaling pathway / cytokine activity / cholesterol homeostasis / lipopolysaccharide binding / positive regulation of smooth muscle cell proliferation / NOD1/2 Signaling Pathway / positive regulation of inflammatory response / positive regulation of non-canonical NF-kappaB signal transduction / cellular response to amyloid-beta / positive regulation of type II interferon production / positive regulation of neuron apoptotic process / cell-cell signaling / positive regulation of cold-induced thermogenesis / positive regulation of NF-kappaB transcription factor activity / regulation of inflammatory response / cellular response to lipopolysaccharide / angiogenesis / Interleukin-4 and Interleukin-13 signaling / cell population proliferation / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / defense response to Gram-positive bacterium / defense response to bacterium / inflammatory response / cysteine-type endopeptidase activity / innate immune response / lipid binding / apoptotic process / endoplasmic reticulum membrane / endoplasmic reticulum / positive regulation of transcription by RNA polymerase II / protein-containing complex / mitochondrion / proteolysis / extracellular space / extracellular region / plasma membrane / cytoplasm / cytosol 類似検索 - 分子機能 | |||||||||
生物種 | ![]() | |||||||||
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: 3.2 Å | |||||||||
![]() | Pascal, D. / Dong, Y. / Wu, H. / Jon, K. | |||||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Structural insights into cytokine cleavage by inflammatory caspase-4. 著者: Pascal Devant / Ying Dong / Julian Mintseris / Weiyi Ma / Steven P Gygi / Hao Wu / Jonathan C Kagan / ![]() 要旨: Inflammatory caspases are key enzymes in mammalian innate immunity that control the processing and release of interleukin-1 (IL-1)-family cytokines. Despite the biological importance, the structural ...Inflammatory caspases are key enzymes in mammalian innate immunity that control the processing and release of interleukin-1 (IL-1)-family cytokines. Despite the biological importance, the structural basis for inflammatory caspase-mediated cytokine processing has remained unclear. To date, catalytic cleavage of IL-1-family members, including pro-IL-1β and pro-IL-18, has been attributed primarily to caspase-1 activities within canonical inflammasomes. Here we demonstrate that the lipopolysaccharide receptor caspase-4 from humans and other mammalian species (except rodents) can cleave pro-IL-18 with an efficiency similar to pro-IL-1β and pro-IL-18 cleavage by the prototypical IL-1-converting enzyme caspase-1. This ability of caspase-4 to cleave pro-IL-18, combined with its previously defined ability to cleave and activate the lytic pore-forming protein gasdermin D (GSDMD), enables human cells to bypass the need for canonical inflammasomes and caspase-1 for IL-18 release. The structure of the caspase-4-pro-IL-18 complex determined using cryogenic electron microscopy reveals that pro-lL-18 interacts with caspase-4 through two distinct interfaces: a protease exosite and an interface at the caspase-4 active site involving residues in the pro-domain of pro-IL-18, including the tetrapeptide caspase-recognition sequence. The mechanisms revealed for cytokine substrate capture and cleavage differ from those observed for the caspase substrate GSDMD. These findings provide a structural framework for the discussion of caspase activities in health and disease. | |||||||||
履歴 |
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構造の表示
構造ビューア | 分子: ![]() ![]() |
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ダウンロードとリンク
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ダウンロード
PDBx/mmCIF形式 | ![]() | 160.3 KB | 表示 | ![]() |
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PDB形式 | ![]() | 124.3 KB | 表示 | ![]() |
PDBx/mmJSON形式 | ![]() | ツリー表示 | ![]() | |
その他 | ![]() |
-検証レポート
文書・要旨 | ![]() | 979.3 KB | 表示 | ![]() |
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文書・詳細版 | ![]() | 979.8 KB | 表示 | |
XML形式データ | ![]() | 32.6 KB | 表示 | |
CIF形式データ | ![]() | 46.9 KB | 表示 | |
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-関連構造データ
関連構造データ | ![]() 40678MC 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 ( |
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類似構造データ | 類似検索 - 機能・相同性 ![]() |
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リンク
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集合体
登録構造単位 | ![]()
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要素
#1: タンパク質 | 分子量: 23353.363 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() ![]() #2: タンパク質 | 分子量: 10770.386 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() ![]() #3: タンパク質 | 分子量: 21850.641 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() 発現宿主: ![]() 参照: UniProt: Q14116 |
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-実験情報
-実験
実験 | 手法: 電子顕微鏡法 |
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EM実験 | 試料の集合状態: PARTICLE / 3次元再構成法: 単粒子再構成法 |
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試料調製
構成要素 | 名称: caspase-4 in complex with pro-IL-18 / タイプ: COMPLEX / Entity ID: #1, #3, #2 / 由来: MULTIPLE SOURCES |
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分子量 | 値: 0.144 MDa / 実験値: YES |
由来(天然) | 生物種: ![]() |
由来(組換発現) | 生物種: ![]() ![]() |
緩衝液 | pH: 7.4 |
試料 | 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES |
急速凍結 | 凍結剤: ETHANE |
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電子顕微鏡撮影
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |
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顕微鏡 | モデル: FEI TITAN KRIOS |
電子銃 | 電子線源: ![]() |
電子レンズ | モード: BRIGHT FIELD / 最大 デフォーカス(公称値): 2500 nm / 最小 デフォーカス(公称値): 1000 nm |
撮影 | 電子線照射量: 55 e/Å2 / フィルム・検出器のモデル: GATAN K3 (6k x 4k) |
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解析
CTF補正 | タイプ: NONE | ||||||||||||||||||||||||
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3次元再構成 | 解像度: 3.2 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 200000 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
拘束条件 |
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