+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-20186 | |||||||||
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タイトル | Cryo-EM structure of the N-terminally acetylated C-terminal Alpha-synuclein truncation Ac1-103 | |||||||||
マップデータ | em-volume_P1 | |||||||||
試料 |
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キーワード | C-terminal Alpha-synuclein truncation / 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 / 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 / positive regulation of exocytosis / synaptic vesicle 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 / synapse organization / regulation of long-term neuronal synaptic plasticity / microglial cell activation / 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 / histone binding / cellular response to oxidative stress / 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 | 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 | Xiaodan N / Ryan PM | |||||||||
資金援助 | 米国, 1件
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引用 | ジャーナル: J Mol Biol / 年: 2019 タイトル: Structural Insights into α-Synuclein Fibril Polymorphism: Effects of Parkinson's Disease-Related C-Terminal Truncations. 著者: Xiaodan Ni / Ryan P McGlinchey / Jiansen Jiang / Jennifer C Lee / 要旨: Lewy bodies, hallmarks of Parkinson's disease, contain C-terminally truncated (ΔC) α-synuclein (α-syn). Here, we report fibril structures of three N-terminally acetylated (Ac) α-syn constructs, ...Lewy bodies, hallmarks of Parkinson's disease, contain C-terminally truncated (ΔC) α-synuclein (α-syn). Here, we report fibril structures of three N-terminally acetylated (Ac) α-syn constructs, Ac1-140, Ac1-122, and Ac1-103, solved by cryoelectron microscopy. Both ΔC-α-syn variants exhibited faster aggregation kinetics, and Ac1-103 fibrils efficiently seeded the full-length protein, highlighting their importance in pathogenesis. Interestingly, fibril helical twists increased upon the removal of C-terminal residues and can be propagated through cross-seeding. Compared to that of Ac1-140, increased electron densities were seen in the N-terminus of Ac1-103, whereas the C-terminus of Ac1-122 appeared more structured. In accord, the respective termini of ΔC-α-syn exhibited increased protease resistance. Despite similar amyloid core residues, distinctive features were seen for both Ac1-122 and Ac1-103. Particularly, Ac1-103 has the tightest packed core with an additional turn, likely attributable to conformational changes in the N-terminal region. These molecular differences offer insights into the effect of C-terminal truncations on α-syn fibril polymorphism. | |||||||||
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_20186.map.gz | 28.4 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-20186-v30.xml emd-20186.xml | 9.3 KB 9.3 KB | 表示 表示 | EMDBヘッダ |
FSC (解像度算出) | emd_20186_fsc.xml | 7.2 KB | 表示 | FSCデータファイル |
画像 | emd_20186.png | 72.3 KB | ||
Filedesc metadata | emd-20186.cif.gz | 4.8 KB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-20186 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-20186 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_20186_validation.pdf.gz | 616.6 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_20186_full_validation.pdf.gz | 616.2 KB | 表示 | |
XML形式データ | emd_20186_validation.xml.gz | 9.7 KB | 表示 | |
CIF形式データ | emd_20186_validation.cif.gz | 12.4 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-20186 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-20186 | 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_20186.map.gz / 形式: CCP4 / 大きさ: 30.5 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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注釈 | em-volume_P1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 1.06 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 : N-terminally acetylated C-terminal Alpha-synuclein truncation Ac1-103
全体 | 名称: N-terminally acetylated C-terminal Alpha-synuclein truncation Ac1-103 |
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要素 |
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-超分子 #1: N-terminally acetylated C-terminal Alpha-synuclein truncation Ac1-103
超分子 | 名称: N-terminally acetylated C-terminal Alpha-synuclein truncation Ac1-103 タイプ: organelle_or_cellular_component / ID: 1 / 親要素: 0 / 含まれる分子: all |
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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: 14.476108 KDa |
組換発現 | 生物種: Escherichia coli (大腸菌) |
配列 | 文字列: MDVFMKGLSK AKEGVVAAAE KTKQGVAEAA GKTKEGVLYV GSKTKEGVVH GVATVAEKTK EQVTNVGGAV VTGVTAVAQK TVEGAGSIA AATGFVKKDQ LGKNEEGAPQ EGILEDMPVD PDNEAYEMPS EEGYQDYEPE A 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
緩衝液 | pH: 7.4 |
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凍結 | 凍結剤: ETHANE |
-電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
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撮影 | フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) 検出モード: SUPER-RESOLUTION / 平均電子線量: 1.3 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 |