+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 6ncv | |||||||||
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タイトル | Cryo-EM structure of NLRP6 PYD filament | |||||||||
要素 | NACHT, LRR and PYD domains-containing protein 6 | |||||||||
キーワード | SIGNALING PROTEIN / PROTEIN FIBRIL / death domain fold / helical assembly / inflammasome (インフラマソーム) | |||||||||
機能・相同性 | 機能・相同性情報 non-membrane-bounded organelle / regulation of mucus secretion / NLRP6 inflammasome complex assembly / neutrophil-mediated killing of gram-positive bacterium / NLRP6 inflammasome complex / positive regulation of interleukin-18-mediated signaling pathway / lipoteichoic acid binding / host-mediated regulation of intestinal microbiota composition / vasopressin receptor activity / acute inflammatory response to antigenic stimulus ...non-membrane-bounded organelle / regulation of mucus secretion / NLRP6 inflammasome complex assembly / neutrophil-mediated killing of gram-positive bacterium / NLRP6 inflammasome complex / positive regulation of interleukin-18-mediated signaling pathway / lipoteichoic acid binding / host-mediated regulation of intestinal microbiota composition / vasopressin receptor activity / acute inflammatory response to antigenic stimulus / negative regulation of toll-like receptor signaling pathway / canonical inflammasome complex / acute inflammatory response / pattern recognition receptor activity / pyroptosis / antiviral innate immune response / necroptotic process / negative regulation of type II interferon production / signaling adaptor activity / negative regulation of canonical NF-kappaB signal transduction / negative regulation of inflammatory response to antigenic stimulus / molecular condensate scaffold activity / regulation of autophagy / lipopolysaccharide binding / response to bacterium / peptide binding / wound healing / protein homooligomerization / negative regulation of ERK1 and ERK2 cascade / positive regulation of inflammatory response / double-stranded RNA binding / regulation of inflammatory response / defense response to virus / 核膜 / defense response to Gram-positive bacterium / ATP binding / 細胞膜 / 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: 3.7 Å | |||||||||
データ登録者 | Shen, C. / Fu, T.M. / Wu, H. | |||||||||
資金援助 | 米国, 2件
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引用 | ジャーナル: Proc Natl Acad Sci U S A / 年: 2019 タイトル: Molecular mechanism for NLRP6 inflammasome assembly and activation. 著者: Chen Shen / Alvin Lu / Wen Jun Xie / Jianbin Ruan / Roberto Negro / Edward H Egelman / Tian-Min Fu / Hao Wu / 要旨: Inflammasomes are large protein complexes that trigger host defense in cells by activating inflammatory caspases for cytokine maturation and pyroptosis. NLRP6 is a sensor protein in the nucleotide- ...Inflammasomes are large protein complexes that trigger host defense in cells by activating inflammatory caspases for cytokine maturation and pyroptosis. NLRP6 is a sensor protein in the nucleotide-binding domain (NBD) and leucine-rich repeat (LRR)-containing (NLR) inflammasome family that has been shown to play multiple roles in regulating inflammation and host defenses. Despite the significance of the NLRP6 inflammasome, little is known about the molecular mechanism behind its assembly and activation. Here we present cryo-EM and crystal structures of NLRP6 pyrin domain (PYD). We show that NLRP6 PYD alone is able to self-assemble into filamentous structures accompanied by large conformational changes and can recruit the ASC adaptor using PYD-PYD interactions. Using molecular dynamics simulations, we identify the surface that the NLRP6 PYD filament uses to recruit ASC PYD. We further find that full-length NLRP6 assembles in a concentration-dependent manner into wider filaments with a PYD core surrounded by the NBD and the LRR domain. These findings provide a structural understanding of inflammasome assembly by NLRP6 and other members of the NLR family. | |||||||||
履歴 |
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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 | 6ncv.cif.gz | 329.8 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb6ncv.ent.gz | 275.1 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 6ncv.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/nc/6ncv ftp://data.pdbj.org/pub/pdb/validation_reports/nc/6ncv | HTTPS FTP |
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-関連構造データ
-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: 3 / Dyad axis: no / N subunits divisor: 1 / Num. of operations: 21 / Rise per n subunits: 13.8 Å / Rotation per n subunits: 56.8 °) |
-要素
#1: タンパク質 | 分子量: 11931.579 Da / 分子数: 21 / 断片: PYD domain (UNP residues 1-106) / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: NLRP6, NALP6, PYPAF5 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) 参照: UniProt: P59044 |
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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: FILAMENT / 3次元再構成法: らせん対称体再構成法 |
-試料調製
構成要素 | 名称: NLRP6 PYD / 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: Spodoptera frugiperda (ツマジロクサヨトウ) |
緩衝液 | pH: 7.4 |
試料 | 濃度: 1.5 mg/ml / 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES |
試料支持 | 詳細: unspecified |
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 |
撮影 | 電子線照射量: 50 e/Å2 フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) |
-解析
CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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らせん対称 | 回転角度/サブユニット: 56.8 ° / 軸方向距離/サブユニット: 13.8 Å / らせん対称軸の対称性: C3 |
3次元再構成 | 解像度: 3.7 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 181477 / 対称性のタイプ: HELICAL |