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基本情報
登録情報 | データベース: PDB / ID: 7pzd | ||||||
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タイトル | Cryo-EM structure of the NLRP3 PYD filament | ||||||
![]() | NACHT, LRR and PYD domains-containing protein 3 | ||||||
![]() | IMMUNE SYSTEM / NLRP3 / Pyrin domain / filament | ||||||
機能・相同性 | ![]() small molecule sensor activity / detection of biotic stimulus / cysteine-type endopeptidase activator activity / phosphatidylinositol phosphate binding / 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 / positive regulation of type 2 immune response / NLRP3 inflammasome complex ...small molecule sensor activity / detection of biotic stimulus / cysteine-type endopeptidase activator activity / phosphatidylinositol phosphate binding / 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 / positive regulation of type 2 immune response / NLRP3 inflammasome complex / 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 / 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 / negative regulation of acute inflammatory response / The NLRP3 inflammasome / protein maturation / Purinergic signaling in leishmaniasis infection / signaling adaptor activity / molecular condensate scaffold activity / positive regulation of interleukin-1 beta production / 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 / 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 / sequence-specific DNA binding / molecular adaptor activity / inflammatory response / Golgi membrane / innate immune response / 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 / ATP binding / identical protein binding / membrane / nucleus / cytoplasm / cytosol 類似検索 - 分子機能 | ||||||
生物種 | ![]() | ||||||
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: 3.6 Å | ||||||
![]() | Hochheiser, I.V. / Hagelueken, G. / Behrmann, H. / Behrmann, E. / Geyer, M. | ||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Directionality of PYD filament growth determined by the transition of NLRP3 nucleation seeds to ASC elongation. 著者: Inga V Hochheiser / Heide Behrmann / Gregor Hagelueken / Juan F Rodríguez-Alcázar / Anja Kopp / Eicke Latz / Elmar Behrmann / Matthias Geyer / ![]() ![]() 要旨: Inflammasomes sense intrinsic and extrinsic danger signals to trigger inflammatory responses and pyroptotic cell death. Homotypic pyrin domain (PYD) interactions of inflammasome forming nucleotide- ...Inflammasomes sense intrinsic and extrinsic danger signals to trigger inflammatory responses and pyroptotic cell death. Homotypic pyrin domain (PYD) interactions of inflammasome forming nucleotide-binding oligomerization domain (NOD)-like receptors with the adaptor protein ASC (apoptosis-associated speck-like protein containing a CARD) mediate oligomerization into filamentous assemblies. We describe the cryo-electron microscopy (cryo-EM) structure of the human NLRP3 filament and identify a pattern of highly polar interface residues that form the homomeric interactions leading to characteristic filament ends designated as A- and B-ends. Coupling a titration polymerization assay to cryo-EM, we demonstrate that ASC adaptor protein elongation on NLRP3 nucleation seeds is unidirectional, associating exclusively to the B-end of the filament. Notably, NLRP3 and ASC PYD filaments exhibit the same symmetry in rotation and axial rise per subunit, allowing a continuous transition between NLRP3 and ASC. Integrating the directionality of filament growth, we present a molecular model of the ASC speck consisting of active NLRP3, ASC, and Caspase-1 proteins. | ||||||
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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PDBx/mmCIF形式 | ![]() | 406.1 KB | 表示 | ![]() |
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PDB形式 | ![]() | 328.4 KB | 表示 | ![]() |
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-検証レポート
文書・要旨 | ![]() | 950.9 KB | 表示 | ![]() |
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文書・詳細版 | ![]() | 967.9 KB | 表示 | |
XML形式データ | ![]() | 34.7 KB | 表示 | |
CIF形式データ | ![]() | 58.6 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 | ![]() 13727MC 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: 12486.243 Da / 分子数: 18 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() ![]() |
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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 |
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試料調製
構成要素 | 名称: filament formed by the human NLRP3 Pyrin domain / タイプ: ORGANELLE OR CELLULAR COMPONENT / Entity ID: all / 由来: RECOMBINANT |
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分子量 | 実験値: NO |
由来(天然) | 生物種: ![]() |
由来(組換発現) | 生物種: ![]() ![]() |
緩衝液 | pH: 7.5 / 詳細: 20 mM HEPES (pH 7.5), 150 mM NaCl, 0.5 mM TCEP |
試料 | 濃度: 1 mg/ml / 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES |
試料支持 | グリッドの材料: COPPER / グリッドのサイズ: 300 divisions/in. / グリッドのタイプ: Quantifoil R1.2/1.3 |
急速凍結 | 装置: LEICA EM GP / 凍結剤: ETHANE / 湿度: 80 % / 凍結前の試料温度: 293 K |
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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: TUNGSTEN HAIRPIN / 加速電圧: 300 kV / 照射モード: FLOOD BEAM |
電子レンズ | モード: BRIGHT FIELD |
試料ホルダ | 凍結剤: NITROGEN 試料ホルダーモデル: FEI TITAN KRIOS AUTOGRID HOLDER |
撮影 | 電子線照射量: 60 e/Å2 フィルム・検出器のモデル: FEI FALCON II (4k x 4k) |
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解析
EMソフトウェア | 名称: RELION / カテゴリ: 3次元再構成 |
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CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION |
らせん対称 | 回転角度/サブユニット: 54.88 ° / 軸方向距離/サブユニット: 14.32 Å / らせん対称軸の対称性: C3 |
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: 60333 / 対称性のタイプ: HELICAL |