+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 8ert | ||||||
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タイトル | NLRP3 PYD filament | ||||||
要素 | NACHT, LRR and PYD domains-containing protein 3 | ||||||
キーワード | IMMUNE SYSTEM (免疫系) / inflammasome (インフラマソーム) / cytosolic protein (細胞質基質) / cytosolic protein-transferase complex (細胞質基質) | ||||||
機能・相同性 | 機能・相同性情報 small molecule sensor activity / detection of biotic stimulus / phosphatidylinositol phosphate binding / cysteine-type endopeptidase activator activity / positive regulation of T-helper 2 cell differentiation / NLRP3 inflammasome complex assembly / interphase microtubule organizing center / positive regulation of T-helper 2 cell cytokine production / NLRP3 inflammasome complex / positive regulation of type 2 immune response ...small molecule sensor activity / detection of biotic stimulus / phosphatidylinositol phosphate binding / cysteine-type endopeptidase activator activity / positive regulation of T-helper 2 cell differentiation / NLRP3 inflammasome complex assembly / interphase microtubule organizing center / positive regulation of T-helper 2 cell cytokine production / NLRP3 inflammasome complex / positive regulation of type 2 immune response / peptidoglycan binding / osmosensory signaling pathway / negative regulation of non-canonical NF-kappaB signal transduction / phosphatidylinositol-4-phosphate binding / negative regulation of interleukin-1 beta production / 微小管形成中心 / pattern recognition receptor signaling pathway / negative regulation of NF-kappaB transcription factor activity / positive regulation of interleukin-4 production / pyroptotic inflammatory response / negative regulation of acute inflammatory response / positive regulation of cysteine-type endopeptidase activity involved in apoptotic process / protein maturation / The NLRP3 inflammasome / Purinergic signaling in leishmaniasis infection / 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 / ADP binding / Cytoprotection by HMOX1 / Metalloprotease DUBs / cellular response to virus / defense response / negative regulation of inflammatory response / positive regulation of inflammatory response / positive regulation of non-canonical NF-kappaB signal transduction / SARS-CoV-1 activates/modulates innate immune responses / positive regulation of NF-kappaB transcription factor activity / DNA-binding transcription factor binding / cellular response to lipopolysaccharide / sequence-specific DNA binding / molecular adaptor activity / 炎症 / ゴルジ体 / 自然免疫系 / apoptotic process / SARS-CoV-2 activates/modulates innate and adaptive immune responses / 小胞体 / シグナル伝達 / ATP hydrolysis activity / positive regulation of transcription by RNA polymerase II / ミトコンドリア / extracellular region / ATP binding / 生体膜 / identical protein 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 / 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.3 Å | ||||||
データ登録者 | Wu, H. / Xiao, L. | ||||||
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 | 8ert.cif.gz | 463.5 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb8ert.ent.gz | 372.2 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 8ert.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/er/8ert ftp://data.pdbj.org/pub/pdb/validation_reports/er/8ert | HTTPS FTP |
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-関連構造データ
関連構造データ | 28560MC 8ej4C 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: 11146.940 Da / 分子数: 21 / 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 |
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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: all / 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 FIELDBright-field microscopy / 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: 3.3 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 33227 / 対称性のタイプ: POINT |