+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 6cu7 | ||||||||||||
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タイトル | Alpha Synuclein fibril formed by full length protein - Rod Polymorph | ||||||||||||
要素 | Alpha-synuclein | ||||||||||||
キーワード | PROTEIN FIBRIL / Parkinson's disease / Synucleinopathy / Amyloid aggregation / Fibril polymorphism | ||||||||||||
機能・相同性 | 機能・相同性情報 negative regulation of mitochondrial electron transport, NADH to ubiquinone / neutral lipid metabolic process / regulation of phospholipase activity / negative regulation of monooxygenase activity / regulation of acyl-CoA biosynthetic process / negative regulation of dopamine uptake involved in synaptic transmission / negative regulation of norepinephrine uptake / positive regulation of glutathione peroxidase activity / positive regulation of SNARE complex assembly / positive regulation of hydrogen peroxide catabolic process ...negative regulation of mitochondrial electron transport, NADH to ubiquinone / neutral lipid metabolic process / regulation of phospholipase activity / negative regulation of monooxygenase activity / regulation of acyl-CoA biosynthetic process / negative regulation of dopamine uptake involved in synaptic transmission / negative regulation of norepinephrine uptake / positive regulation of glutathione peroxidase activity / positive regulation of SNARE complex assembly / positive regulation of hydrogen peroxide catabolic process / supramolecular fiber / negative regulation of transporter activity / mitochondrial membrane organization / negative regulation of chaperone-mediated autophagy / regulation of reactive oxygen species biosynthetic process / positive regulation of protein localization to cell periphery / regulation of synaptic vesicle recycling / negative regulation of platelet-derived growth factor receptor signaling pathway / negative regulation of exocytosis / regulation of glutamate secretion / regulation of norepinephrine uptake / response to iron(II) ion / SNARE complex assembly / positive regulation of neurotransmitter secretion / dopamine biosynthetic process / regulation of locomotion / positive regulation of inositol phosphate biosynthetic process / synaptic vesicle priming / regulation of macrophage activation / negative regulation of microtubule polymerization / dopamine uptake involved in synaptic transmission / synaptic vesicle transport / dynein complex binding / positive regulation of receptor recycling / regulation of dopamine secretion / protein kinase inhibitor activity / negative regulation of thrombin-activated receptor signaling pathway / response to type II interferon / cuprous ion binding / synaptic vesicle exocytosis / positive regulation of exocytosis / kinesin binding / positive regulation of endocytosis / mitochondrial ATP synthesis coupled electron transport / cysteine-type endopeptidase inhibitor activity involved in apoptotic process / response to magnesium ion / regulation of presynapse assembly / synaptic vesicle endocytosis / negative regulation of serotonin uptake / alpha-tubulin binding / localization / phospholipid metabolic process / supramolecular fiber organization / axon terminus / inclusion body / cellular response to copper ion / cellular response to epinephrine stimulus / Hsp70 protein binding / excitatory postsynaptic potential / response to interleukin-1 / adult locomotory behavior / SNARE binding / positive regulation of release of sequestered calcium ion into cytosol / fatty acid metabolic process / long-term synaptic potentiation / phosphoprotein binding / protein tetramerization / regulation of transmembrane transporter activity / microglial cell activation / synapse organization / regulation of long-term neuronal synaptic plasticity / negative regulation of protein kinase activity / protein destabilization / negative regulation of cysteine-type endopeptidase activity involved in apoptotic process / ferrous iron binding / tau protein binding / PKR-mediated signaling / positive regulation of protein serine/threonine kinase activity / receptor internalization / phospholipid binding / synaptic vesicle membrane / positive regulation of inflammatory response / activation of cysteine-type endopeptidase activity involved in apoptotic process / actin cytoskeleton / positive regulation of peptidyl-serine phosphorylation / actin binding / cell cortex / cellular response to oxidative stress / histone binding / growth cone / postsynapse / chemical synaptic transmission / neuron apoptotic process / negative regulation of neuron apoptotic process / amyloid fibril formation / response to lipopolysaccharide / molecular adaptor activity / oxidoreductase activity / lysosome / transcription cis-regulatory region binding 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: 3.5 Å | ||||||||||||
データ登録者 | Li, B. / Hatami, A. / Ge, P. / Murray, K.A. / Sheth, P. / Zhang, M. / Nair, G. / Sawaya, M.R. / Zhu, C. / Broad, M. ...Li, B. / Hatami, A. / Ge, P. / Murray, K.A. / Sheth, P. / Zhang, M. / Nair, G. / Sawaya, M.R. / Zhu, C. / Broad, M. / Shin, W.S. / Ye, S. / John, V. / Eisenberg, D.S. / Zhou, Z.H. / Jiang, L. | ||||||||||||
資金援助 | 米国, 3件
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引用 | ジャーナル: Nat Commun / 年: 2018 タイトル: Cryo-EM of full-length α-synuclein reveals fibril polymorphs with a common structural kernel. 著者: Binsen Li / Peng Ge / Kevin A Murray / Phorum Sheth / Meng Zhang / Gayatri Nair / Michael R Sawaya / Woo Shik Shin / David R Boyer / Shulin Ye / David S Eisenberg / Z Hong Zhou / Lin Jiang / 要旨: α-Synuclein (aSyn) fibrillar polymorphs have distinct in vitro and in vivo seeding activities, contributing differently to synucleinopathies. Despite numerous prior attempts, how polymorphic aSyn ...α-Synuclein (aSyn) fibrillar polymorphs have distinct in vitro and in vivo seeding activities, contributing differently to synucleinopathies. Despite numerous prior attempts, how polymorphic aSyn fibrils differ in atomic structure remains elusive. Here, we present fibril polymorphs from the full-length recombinant human aSyn and their seeding capacity and cytotoxicity in vitro. By cryo-electron microscopy helical reconstruction, we determine the structures of the two predominant species, a rod and a twister, both at 3.7 Å resolution. Our atomic models reveal that both polymorphs share a kernel structure of a bent β-arch, but differ in their inter-protofilament interfaces. Thus, different packing of the same kernel structure gives rise to distinct fibril polymorphs. Analyses of disease-related familial mutations suggest their potential contribution to the pathogenesis of synucleinopathies by altering population distribution of the fibril polymorphs. Drug design targeting amyloid fibrils in neurodegenerative diseases should consider the formation and distribution of concurrent fibril polymorphs. | ||||||||||||
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 | 6cu7.cif.gz | 109.2 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb6cu7.ent.gz | 80.2 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 6cu7.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 | 6cu7_validation.pdf.gz | 1018 KB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 6cu7_full_validation.pdf.gz | 1019.9 KB | 表示 | |
XML形式データ | 6cu7_validation.xml.gz | 17.4 KB | 表示 | |
CIF形式データ | 6cu7_validation.cif.gz | 26.9 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/cu/6cu7 ftp://data.pdbj.org/pub/pdb/validation_reports/cu/6cu7 | HTTPS FTP |
-関連構造データ
-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: 14476.108 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: SNCA, NACP, PARK1 / 発現宿主: Escherichia coli (大腸菌) / 株 (発現宿主): BL21-DE3 Gold / 参照: UniProt: P37840 |
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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: Alpha-synuclein fibril - rod polymorph / タイプ: COMPLEX / Entity ID: all / 由来: RECOMBINANT |
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分子量 | 単位: MEGADALTONS / 実験値: NO |
由来(天然) | 生物種: Homo sapiens (ヒト) |
由来(組換発現) | 生物種: Escherichia coli (大腸菌) / 株: BL21-DE3 Gold |
緩衝液 | pH: 3 |
緩衝液成分 | 濃度: 15 mM / 名称: tetrabutylphosphonium bromide / 式: C16H36BrP |
試料 | 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES |
試料支持 | 詳細: Quantifoil grid was treated with 1,2-Dichloroethane for one week, coated with additional carbon, and baken under 120kV in Camera chamber for 3 days グリッドの材料: COPPER / グリッドのサイズ: 200 divisions/in. / グリッドのタイプ: Quantifoil R1.2/1.3 |
急速凍結 | 装置: FEI VITROBOT MARK IV / 凍結剤: ETHANE / 湿度: 100 % / 凍結前の試料温度: 295 K / 詳細: blot force: 1 blot time: 4s |
-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 / 倍率(公称値): 130000 X / 最大 デフォーカス(公称値): 2700 nm / 最小 デフォーカス(公称値): 2700 nm / Calibrated defocus min: 1500 nm / 最大 デフォーカス(補正後): 4000 nm / Cs: 2.7 mm / C2レンズ絞り径: 50 µm / アライメント法: COMA FREE |
試料ホルダ | 凍結剤: NITROGEN 試料ホルダーモデル: FEI TITAN KRIOS AUTOGRID HOLDER 最高温度: 77 K / 最低温度: 77 K |
撮影 | 平均露光時間: 10 sec. / 電子線照射量: 30 e/Å2 / 検出モード: COUNTING フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) 撮影したグリッド数: 1 / 実像数: 1821 / 詳細: Frame rate 5 Hz |
電子光学装置 | エネルギーフィルター名称: GIF Quantum LS / エネルギーフィルター 上限: 10 eV / エネルギーフィルター 下限: -10 eV |
画像スキャン | サンプリングサイズ: 5 µm / 横: 3838 / 縦: 3710 / 動画フレーム数/画像: 50 / 利用したフレーム数/画像: 3-20 |
-解析
ソフトウェア | 名称: PHENIX / バージョン: 1.13_2998: / 分類: 精密化 | ||||||||||||||||||||||||||||||||||||
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EMソフトウェア |
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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: 179.53 ° / 軸方向距離/サブユニット: 2.4 Å / らせん対称軸の対称性: C1 | ||||||||||||||||||||||||||||||||||||
粒子像の選択 | 選択した粒子像数: 182253 | ||||||||||||||||||||||||||||||||||||
3次元再構成 | 解像度: 3.5 Å / 解像度の算出法: FSC 0.5 CUT-OFF / 粒子像の数: 23830 / アルゴリズム: BACK PROJECTION / 対称性のタイプ: HELICAL | ||||||||||||||||||||||||||||||||||||
原子モデル構築 | プロトコル: AB INITIO MODEL / 空間: REAL | ||||||||||||||||||||||||||||||||||||
拘束条件 |
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