+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 8ej4 | ||||||
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タイトル | Cryo-EM structure of the active NLRP3 inflammasome disk | ||||||
要素 |
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キーワード | Immune System/Transferase / Inflammasome / CYTOSOLIC PROTEIN / Immune System-Transferase complex | ||||||
機能・相同性 | 機能・相同性情報 NEK6-subfamily protein kinase / small molecule sensor activity / detection of biotic stimulus / cysteine-type endopeptidase activator activity / phosphatidylinositol phosphate binding / positive regulation of T-helper 2 cell differentiation / Activation of NIMA Kinases NEK9, NEK6, NEK7 / NLRP3 inflammasome complex assembly / interphase microtubule organizing center / positive regulation of T-helper 2 cell cytokine production ...NEK6-subfamily protein kinase / small molecule sensor activity / detection of biotic stimulus / cysteine-type endopeptidase activator activity / phosphatidylinositol phosphate binding / positive regulation of T-helper 2 cell differentiation / Activation of NIMA Kinases NEK9, NEK6, NEK7 / NLRP3 inflammasome complex assembly / interphase microtubule organizing center / positive regulation of T-helper 2 cell cytokine production / positive regulation of type 2 immune response / cellular response to potassium ion / NLRP3 inflammasome complex / Nuclear Pore Complex (NPC) Disassembly / peptidoglycan binding / osmosensory signaling pathway / phosphatidylinositol-4-phosphate binding / negative regulation of non-canonical NF-kappaB signal transduction / pattern recognition receptor signaling pathway / negative regulation of interleukin-1 beta production / microtubule organizing center / positive regulation of NLRP3 inflammasome complex assembly / negative regulation of NF-kappaB transcription factor activity / positive regulation of interleukin-4 production / pyroptotic inflammatory response / positive regulation of cysteine-type endopeptidase activity involved in apoptotic process / positive regulation of telomere capping / negative regulation of acute inflammatory response / The NLRP3 inflammasome / protein maturation / spindle assembly / Purinergic signaling in leishmaniasis infection / signaling adaptor activity / EML4 and NUDC in mitotic spindle formation / : / positive regulation of telomere maintenance via telomerase / regulation of mitotic cell cycle / molecular condensate scaffold activity / positive regulation of interleukin-1 beta production / molecular function activator 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 / Cytoprotection by HMOX1 / Metalloprotease DUBs / cellular response to virus / ADP binding / defense response / negative regulation of inflammatory response / spindle pole / positive regulation of inflammatory response / positive regulation of non-canonical NF-kappaB signal transduction / SARS-CoV-1 activates/modulates innate immune responses / protein-macromolecule adaptor activity / positive regulation of NF-kappaB transcription factor activity / cellular response to lipopolysaccharide / DNA-binding transcription factor binding / microtubule / sequence-specific DNA binding / molecular adaptor activity / inflammatory response / Golgi membrane / protein phosphorylation / innate immune response / protein serine kinase activity / protein serine/threonine kinase activity / centrosome / apoptotic process / SARS-CoV-2 activates/modulates innate and adaptive immune responses / endoplasmic reticulum / signal transduction / ATP hydrolysis activity / positive regulation of transcription by RNA polymerase II / mitochondrion / extracellular region / nucleoplasm / ATP binding / identical protein binding / membrane / nucleus / metal ion binding / cytoplasm / cytosol 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: 3.4 Å | ||||||
データ登録者 | Hao, W. / Le, X. | ||||||
資金援助 | 米国, 1件
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引用 | ジャーナル: Nature / 年: 2023 タイトル: Cryo-EM structures of the active NLRP3 inflammasome disc. 著者: Le Xiao / Venkat Giri Magupalli / Hao Wu / 要旨: Inflammasomes are cytosolic innate immune complexes that activate caspase-1 following detection of pathogenic and endogenous dangers, and NACHT-, leucine-rich repeat (LRR)- and pyrin domain (PYD)- ...Inflammasomes are cytosolic innate immune complexes that activate caspase-1 following detection of pathogenic and endogenous dangers, and NACHT-, leucine-rich repeat (LRR)- and pyrin domain (PYD)-containing protein 3 (NLRP3) is an inflammasome sensor of membrane damage highly important in regard to the induction of inflammation. Here we report cryogenic electron microscopy structures of disc-shaped active NLRP3 oligomers in complex with adenosine 5'-O-(3-thio)triphosphate, the centrosomal NIMA-related kinase 7 (NEK7) and the adaptor protein ASC, which recruits caspase-1. In these NLRP3-NEK7-ASC complexes, the central NACHT domain of NLRP3 assumes an ATP-bound conformation in which two of its subdomains rotate by about 85° relative to the ADP-bound inactive conformation. The fish-specific NACHT-associated domain conserved in NLRP3 but absent in most NLRPs becomes ordered in its key regions to stabilize the active NACHT conformation and mediate most interactions in the disc. Mutations on these interactions compromise NLRP3-mediated caspase-1 activation. The N-terminal PYDs from all NLRP3 subunits combine to form a PYD filament that recruits ASC PYD to elicit downstream signalling. Surprisingly, the C-terminal LRR domain and the LRR-bound NEK7 do not participate in disc interfaces. Together with previous structures of an inactive NLRP3 cage in which LRR-LRR interactions play an important role, we propose that the role of NEK7 is to break the inactive cage to transform NLRP3 into the active NLRP3 inflammasome disc. | ||||||
履歴 |
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-構造の表示
構造ビューア | 分子: MolmilJmol/JSmol |
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-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 8ej4.cif.gz | 2.1 MB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb8ej4.ent.gz | 表示 | PDB形式 | |
PDBx/mmJSON形式 | 8ej4.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
文書・要旨 | 8ej4_validation.pdf.gz | 2.1 MB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 8ej4_full_validation.pdf.gz | 2.8 MB | 表示 | |
XML形式データ | 8ej4_validation.xml.gz | 387.6 KB | 表示 | |
CIF形式データ | 8ej4_validation.cif.gz | 551.4 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/ej/8ej4 ftp://data.pdbj.org/pub/pdb/validation_reports/ej/8ej4 | HTTPS FTP |
-関連構造データ
関連構造データ | 28175MC 8ertC 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 | 類似検索 - 機能・相同性F&H 検索 |
-リンク
-集合体
登録構造単位 |
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1 |
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-要素
#1: タンパク質 | 分子量: 102675.570 Da / 分子数: 10 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: NLRP3, C1orf7, CIAS1, NALP3, PYPAF1 / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: Q96P20 #2: タンパク質 | 分子量: 32038.203 Da / 分子数: 10 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: NEK7 / 発現宿主: Homo sapiens (ヒト) 参照: UniProt: Q8TDX7, non-specific serine/threonine protein kinase #3: 化合物 | ChemComp-AGS / #4: 化合物 | ChemComp-MG / 研究の焦点であるリガンドがあるか | Y | |
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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 |
-試料調製
構成要素 | 名称: a complex of NLRP3 and NEK7 / タイプ: COMPLEX / Entity ID: #1-#2 / 由来: RECOMBINANT |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
由来(組換発現) | 生物種: Homo sapiens (ヒト) |
緩衝液 | pH: 8 |
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 |
-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: FIELD EMISSION GUN / 加速電圧: 300 kV / 照射モード: FLOOD BEAM |
電子レンズ | モード: BRIGHT FIELD / 最大 デフォーカス(公称値): 2000 nm / 最小 デフォーカス(公称値): 1000 nm |
撮影 | 電子線照射量: 50 e/Å2 / フィルム・検出器のモデル: GATAN K3 (6k x 4k) |
-解析
CTF補正 | タイプ: NONE |
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3次元再構成 | 解像度: 3.4 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 51576 / 対称性のタイプ: POINT |