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データを開く
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基本情報
登録情報 | データベース: PDB / ID: 8fvu | ||||||
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タイトル | Cryo-EM structure of human Needle/NAIP/NLRC4 (R288A) | ||||||
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![]() | IMMUNE SYSTEM / NLRC4 / NAIP / Inflammasome | ||||||
機能・相同性 | ![]() anthrax lethal factor endopeptidase / IPAF inflammasome complex / The IPAF inflammasome / icosanoid biosynthetic process / canonical inflammasome complex / type III protein secretion system complex / caspase binding / positive regulation of protein processing / protein secretion by the type III secretion system / cysteine-type endopeptidase inhibitor activity involved in apoptotic process ...anthrax lethal factor endopeptidase / IPAF inflammasome complex / The IPAF inflammasome / icosanoid biosynthetic process / canonical inflammasome complex / type III protein secretion system complex / caspase binding / positive regulation of protein processing / protein secretion by the type III secretion system / cysteine-type endopeptidase inhibitor activity involved in apoptotic process / pattern recognition receptor signaling pathway / host cell cytosol / TP53 Regulates Transcription of Caspase Activators and Caspases / pyroptotic inflammatory response / Uptake and function of anthrax toxins / cysteine-type endopeptidase inhibitor activity / endopeptidase activator activity / negative regulation of tumor necrosis factor-mediated signaling pathway / detection of bacterium / activation of innate immune response / protein serine/threonine kinase binding / positive regulation of interleukin-1 beta production / positive regulation of JNK cascade / positive regulation of NF-kappaB transcription factor activity / protein homooligomerization / metalloendopeptidase activity / positive regulation of inflammatory response / metallopeptidase activity / nervous system development / toxin activity / regulation of apoptotic process / basolateral plasma membrane / negative regulation of neuron apoptotic process / defense response to bacterium / positive regulation of apoptotic process / inflammatory response / innate immune response / intracellular membrane-bounded organelle / apoptotic process / negative regulation of apoptotic process / magnesium ion binding / cell surface / protein homodimerization activity / ATP hydrolysis activity / proteolysis / extracellular region / zinc ion binding / ATP binding / metal ion binding / identical protein binding / plasma membrane / cytosol / cytoplasm 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: 3.6 Å | ||||||
![]() | Matico, R.E. / Yu, X. / Miller, R. / Somani, S. / Ricketts, M.D. / Kumar, N. / Steele, R.A. / Medley, Q. / Berger, S. / Faustin, B. / Sharma, S. | ||||||
資金援助 | 1件
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![]() | ![]() タイトル: Structural basis of the human NAIP/NLRC4 inflammasome assembly and pathogen sensing. 著者: Rosalie E Matico / Xiaodi Yu / Robyn Miller / Sandeep Somani / M Daniel Ricketts / Nikit Kumar / Ruth A Steele / Quintus Medley / Scott Berger / Benjamin Faustin / Sujata Sharma / ![]() 要旨: The NLR family caspase activation and recruitment domain-containing 4 (NLRC4) inflammasome is a critical cytosolic innate immune machine formed upon the direct sensing of bacterial infection and in ...The NLR family caspase activation and recruitment domain-containing 4 (NLRC4) inflammasome is a critical cytosolic innate immune machine formed upon the direct sensing of bacterial infection and in response to cell stress during sterile chronic inflammation. Despite its major role in instigating the subsequent host immune response, a more complete understanding of the molecular events in the formation of the NLRC4 inflammasome in humans is lacking. Here we identify Bacillus thailandensis type III secretion system needle protein (Needle) as a potent trigger of the human NLR family apoptosis inhibitory protein (NAIP)/NLRC4 inflammasome complex formation and determine its structural features by cryogenic electron microscopy. We also provide a detailed understanding of how type III secretion system pathogen components are sensed by human NAIP to form a cascade of NLRC4 protomer through a critical lasso-like motif, a 'lock-key' activation model and large structural rearrangement, ultimately forming the full human NLRC4 inflammasome. These results shed light on key regulatory mechanisms specific to the NLRC4 inflammasome assembly, and the innate immune modalities of pathogen sensing in humans. | ||||||
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 | ![]() | 492.8 KB | 表示 | ![]() |
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PDB形式 | ![]() | 384 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 | ![]() | 1.4 MB | 表示 | ![]() |
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文書・詳細版 | ![]() | 1.4 MB | 表示 | |
XML形式データ | ![]() | 69.2 KB | 表示 | |
CIF形式データ | ![]() | 105 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 | ![]() 29493MC ![]() 8fw2C ![]() 8fw9C 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: 160484.359 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() 発現宿主: ![]() ![]() 参照: UniProt: Q13075 | ||
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#2: タンパク質 | 分子量: 116941.531 Da / 分子数: 1 / Mutation: R288A / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() 遺伝子: NLRC4, CARD12, CLAN, CLAN1, IPAF, UNQ6189/PRO20215 発現宿主: ![]() ![]() 参照: UniProt: Q9NPP4 | ||
#3: タンパク質 | 分子量: 42830.836 Da / 分子数: 1 / 由来タイプ: 組換発現 由来: (組換発現) ![]() ![]() ![]() 遺伝子: lef, pXO1-107, BXA0172, GBAA_pXO1_0172, BPSS1548 発現宿主: ![]() ![]() 参照: UniProt: P15917, UniProt: Q63K18, anthrax lethal factor endopeptidase | ||
#4: 化合物 | ChemComp-ATP / | ||
#5: 化合物 | 研究の焦点であるリガンドがあるか | Y | |
-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 |
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由来(天然) |
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由来(組換発現) |
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緩衝液 | pH: 7.5 | ||||||||||||||||||||||||
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
顕微鏡 | モデル: TFS GLACIOS |
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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): 2400 nm / 最小 デフォーカス(公称値): 1200 nm |
撮影 | 電子線照射量: 40 e/Å2 フィルム・検出器のモデル: FEI FALCON IV (4k x 4k) |
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解析
CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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3次元再構成 | 解像度: 3.6 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 106381 / 対称性のタイプ: POINT |