+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-0148 | ||||||||||||
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タイトル | Structure of alpha-synuclein fibrils | ||||||||||||
マップデータ | Structure of alpha-synuclein fibrils | ||||||||||||
試料 |
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キーワード | Parkinson's disease / apha-synuclein / fibril / filament / PROTEIN FIBRIL | ||||||||||||
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 / response to iron(II) ion / regulation of norepinephrine uptake / 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 / synaptic vesicle transport / dopamine uptake involved in synaptic transmission / dynein complex binding / regulation of dopamine secretion / positive regulation of receptor recycling / protein kinase inhibitor activity / negative regulation of thrombin-activated receptor signaling pathway / response to type II interferon / cuprous ion binding / positive regulation of exocytosis / synaptic vesicle exocytosis / positive regulation of endocytosis / kinesin binding / cysteine-type endopeptidase inhibitor activity involved in apoptotic process / response to magnesium ion / synaptic vesicle endocytosis / regulation of presynapse assembly / negative regulation of serotonin uptake / alpha-tubulin binding / phospholipid metabolic process / supramolecular fiber organization / axon terminus / mitochondrial ATP synthesis coupled electron transport / inclusion body / fatty acid metabolic process / cellular response to copper ion / cellular response to epinephrine stimulus / Hsp70 protein binding / response to interleukin-1 / adult locomotory behavior / negative regulation of cysteine-type endopeptidase activity involved in apoptotic process / positive regulation of release of sequestered calcium ion into cytosol / SNARE binding / excitatory postsynaptic potential / long-term synaptic potentiation / phosphoprotein binding / protein tetramerization / regulation of transmembrane transporter activity / synapse organization / microglial cell activation / negative regulation of protein kinase activity / regulation of long-term neuronal synaptic plasticity / protein destabilization / ferrous iron binding / tau protein binding / positive regulation of protein serine/threonine kinase activity / PKR-mediated signaling / receptor internalization / phospholipid binding / activation of cysteine-type endopeptidase activity involved in apoptotic process / synaptic vesicle membrane / positive regulation of inflammatory response / positive regulation of peptidyl-serine phosphorylation / actin cytoskeleton / actin binding / cellular response to oxidative stress / histone binding / cell cortex / growth cone / chemical synaptic transmission / neuron apoptotic process / negative regulation of neuron apoptotic process / transcription cis-regulatory region binding / postsynapse / amyloid fibril formation / response to lipopolysaccharide / molecular adaptor activity / oxidoreductase activity / lysosome / response to xenobiotic stimulus 類似検索 - 分子機能 | ||||||||||||
生物種 | Homo sapiens (ヒト) | ||||||||||||
手法 | らせん対称体再構成法 / クライオ電子顕微鏡法 / 解像度: 3.4 Å | ||||||||||||
データ登録者 | Guerrero-Ferreira R / Taylor NMI | ||||||||||||
引用 | ジャーナル: Elife / 年: 2018 タイトル: Cryo-EM structure of alpha-synuclein fibrils. 著者: Ricardo Guerrero-Ferreira / Nicholas Mi Taylor / Daniel Mona / Philippe Ringler / Matthias E Lauer / Roland Riek / Markus Britschgi / Henning Stahlberg / 要旨: Parkinson's disease is a progressive neuropathological disorder that belongs to the class of synucleinopathies, in which the protein alpha-synuclein is found at abnormally high concentrations in ...Parkinson's disease is a progressive neuropathological disorder that belongs to the class of synucleinopathies, in which the protein alpha-synuclein is found at abnormally high concentrations in affected neurons. Its hallmark are intracellular inclusions called Lewy bodies and Lewy neurites. We here report the structure of cytotoxic alpha-synuclein fibrils (residues 1-121), determined by cryo-electron microscopy at a resolution of 3.4 Å. Two protofilaments form a polar fibril composed of staggered β-strands. The backbone of residues 38 to 95, including the fibril core and the non-amyloid component region, are well resolved in the EM map. Residues 50-57, containing three of the mutation sites associated with familial synucleinopathies, form the interface between the two protofilaments and contribute to fibril stability. A hydrophobic cleft at one end of the fibril may have implications for fibril elongation, and invites for the design of molecules for diagnosis and treatment of synucleinopathies. | ||||||||||||
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 | EMマップ: SurfViewMolmilJmol/JSmol |
添付画像 |
-ダウンロードとリンク
-EMDBアーカイブ
マップデータ | emd_0148.map.gz | 55.3 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-0148-v30.xml emd-0148.xml | 12.1 KB 12.1 KB | 表示 表示 | EMDBヘッダ |
FSC (解像度算出) | emd_0148_fsc.xml | 10 KB | 表示 | FSCデータファイル |
画像 | emd_0148.png | 172.8 KB | ||
Filedesc metadata | emd-0148.cif.gz | 5.5 KB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-0148 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-0148 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_0148_validation.pdf.gz | 498.3 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_0148_full_validation.pdf.gz | 497.8 KB | 表示 | |
XML形式データ | emd_0148_validation.xml.gz | 11.6 KB | 表示 | |
CIF形式データ | emd_0148_validation.cif.gz | 15.2 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-0148 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-0148 | HTTPS FTP |
-関連構造データ
-リンク
EMDBのページ | EMDB (EBI/PDBe) / EMDataResource |
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「今月の分子」の関連する項目 |
-マップ
ファイル | ダウンロード / ファイル: emd_0148.map.gz / 形式: CCP4 / 大きさ: 83.7 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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注釈 | Structure of alpha-synuclein fibrils | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 0.831 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
CCP4マップ ヘッダ情報:
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-添付データ
-試料の構成要素
-全体 : Alpha-synuclein fibrils
全体 | 名称: Alpha-synuclein fibrils |
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要素 |
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-超分子 #1: Alpha-synuclein fibrils
超分子 | 名称: Alpha-synuclein fibrils / タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: all / 詳細: Residues 1-121 |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
-分子 #1: Alpha-synuclein
分子 | 名称: Alpha-synuclein / タイプ: protein_or_peptide / ID: 1 / コピー数: 10 / 光学異性体: LEVO |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 12.242873 KDa |
組換発現 | 生物種: Escherichia coli 'BL21-Gold(DE3)pLysS AG' (大腸菌) |
配列 | 文字列: MDVFMKGLSK AKEGVVAAAE KTKQGVAEAA GKTKEGVLYV GSKTKEGVVH GVATVAEKTK EQVTNVGGAV VTGVTAVAQK TVEGAGSIA AATGFVKKDQ LGKNEEGAPQ EGILEDMPVD PD UniProtKB: Alpha-synuclein |
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
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解析 | らせん対称体再構成法 |
試料の集合状態 | filament |
-試料調製
濃度 | 5 mg/mL | |||||||||||||||
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緩衝液 | pH: 7.3 構成要素:
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グリッド | モデル: Quantifoil R2/2 / 材質: COPPER / メッシュ: 300 / 支持フィルム - 材質: CARBON / 支持フィルム - トポロジー: HOLEY / 前処理 - タイプ: GLOW DISCHARGE / 前処理 - 時間: 20 sec. | |||||||||||||||
凍結 | 凍結剤: ETHANE / チャンバー内湿度: 95 % / チャンバー内温度: 277 K / 装置: FEI VITROBOT MARK IV |
-電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
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特殊光学系 | エネルギーフィルター - 名称: GIF Quantum LS |
撮影 | フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) 検出モード: COUNTING / デジタル化 - 画像ごとのフレーム数: 2-50 / 平均電子線量: 100.0 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: FIELD EMISSION GUN |
電子光学系 | 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELD |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |