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- EMDB-30648: Cryo-EM structure of the hE46K cross-seeded mWT alpha-synuclein fibril -
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基本情報
登録情報 | データベース: EMDB / ID: EMD-30648 | |||||||||
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タイトル | Cryo-EM structure of the hE46K cross-seeded mWT alpha-synuclein fibril | |||||||||
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機能・相同性 | ![]() PKR-mediated signaling / regulation of neurotransmitter secretion / platelet alpha granule membrane / membrane organization / synaptic transmission, dopaminergic / neurotransmitter secretion / neutral lipid metabolic process / regulation of acyl-CoA biosynthetic process / negative regulation of dopamine uptake involved in synaptic transmission / negative regulation of norepinephrine uptake ...PKR-mediated signaling / regulation of neurotransmitter secretion / platelet alpha granule membrane / membrane organization / synaptic transmission, dopaminergic / neurotransmitter secretion / neutral lipid metabolic process / regulation of acyl-CoA biosynthetic process / negative regulation of dopamine uptake involved in synaptic transmission / negative regulation of norepinephrine uptake / response to desipramine / positive regulation of SNARE complex assembly / positive regulation of hydrogen peroxide catabolic process / supramolecular fiber / mitochondrial membrane organization / negative regulation of chaperone-mediated autophagy / negative regulation of platelet-derived growth factor receptor signaling pathway / positive regulation of protein localization to cell periphery / negative regulation of exocytosis / regulation of glutamate secretion / arachidonate binding / regulation of reactive oxygen species metabolic process / dopamine biosynthetic process / SNARE complex assembly / response to iron(II) ion / positive regulation of neurotransmitter secretion / positive regulation of inositol phosphate biosynthetic process / regulation of locomotion / negative regulation of dopamine metabolic process / regulation of macrophage activation / transporter regulator activity / negative regulation of microtubule polymerization / synaptic vesicle transport / synaptic vesicle priming / mitochondrial ATP synthesis coupled electron transport / regulation of dopamine secretion / dynein complex binding / positive regulation of receptor recycling / negative regulation of thrombin-activated receptor signaling pathway / dopamine metabolic process / cuprous ion binding / protein complex oligomerization / nuclear outer membrane / response to magnesium ion / positive regulation of endocytosis / positive regulation of exocytosis / kinesin binding / synaptic vesicle endocytosis / cysteine-type endopeptidase inhibitor activity / negative regulation of serotonin uptake / regulation of neuronal synaptic plasticity / response to type II interferon / regulation of presynapse assembly / alpha-tubulin binding / positive regulation of synaptic transmission / beta-tubulin binding / phospholipase binding / behavioral response to cocaine / cellular response to copper ion / phospholipid metabolic process / cellular response to fibroblast growth factor stimulus / inclusion body / axon terminus / Hsp70 protein binding / response to interleukin-1 / regulation of microtubule cytoskeleton organization / positive regulation of release of sequestered calcium ion into cytosol / SNARE binding / adult locomotory behavior / excitatory postsynaptic potential / phosphoprotein binding / protein tetramerization / microglial cell activation / fatty acid metabolic process / regulation of long-term neuronal synaptic plasticity / ferrous iron binding / synapse organization / protein destabilization / phospholipid binding / receptor internalization / tau protein binding / long-term synaptic potentiation / terminal bouton / positive regulation of inflammatory response / synaptic vesicle membrane / actin cytoskeleton / actin binding / cellular response to oxidative stress / growth cone / cell cortex / histone binding / neuron apoptotic process / response to lipopolysaccharide / microtubule binding / chemical synaptic transmission / mitochondrial outer membrane / negative regulation of neuron apoptotic process / cytoskeleton / oxidoreductase activity / postsynapse 類似検索 - 分子機能 | |||||||||
生物種 | ![]() ![]() | |||||||||
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: 4.5 Å | |||||||||
![]() | Long HF / Sun YP / Liu C | |||||||||
![]() | ![]() タイトル: Wild-type α-synuclein inherits the structure and exacerbated neuropathology of E46K mutant fibril strain by cross-seeding. 著者: Houfang Long / Weitong Zheng / Yang Liu / Yunpeng Sun / Kun Zhao / Zhenying Liu / Wencheng Xia / Shiran Lv / Zhengtao Liu / Dan Li / Kai-Wen He / Cong Liu / ![]() 要旨: Heterozygous point mutations of α-synuclein (α-syn) have been linked to the early onset and rapid progression of familial Parkinson's diseases (fPD). However, the interplay between hereditary ...Heterozygous point mutations of α-synuclein (α-syn) have been linked to the early onset and rapid progression of familial Parkinson's diseases (fPD). However, the interplay between hereditary mutant and wild-type (WT) α-syn and its role in the exacerbated pathology of α-syn in fPD progression are poorly understood. Here, we find that WT mice inoculated with the human E46K mutant α-syn fibril (hE46K) strain develop early-onset motor deficit and morphologically different α-syn aggregation compared with those inoculated with the human WT fibril (hWT) strain. By using cryo-electron microscopy, we reveal at the near-atomic level that the hE46K strain induces both human and mouse WT α-syn monomers to form the fibril structure of the hE46K strain. Moreover, the induced hWT strain inherits most of the pathological traits of the hE46K strain as well. Our work suggests that the structural and pathological features of mutant strains could be propagated by the WT α-syn in such a way that the mutant pathology would be amplified in fPD. | |||||||||
履歴 |
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構造の表示
ムービー |
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構造ビューア | EMマップ: ![]() ![]() ![]() |
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文書・要旨 | ![]() | 342.7 KB | 表示 | ![]() |
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文書・詳細版 | ![]() | 342.3 KB | 表示 | |
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-関連構造データ
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リンク
EMDBのページ | ![]() ![]() |
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「今月の分子」の関連する項目 |
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マップ
ファイル | ![]() | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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投影像・断面図 | 画像のコントロール
画像は Spider により作成 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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
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試料の構成要素
-全体 : the hE46K cross-seeded mWT alpha-synuclein fibril
全体 | 名称: the hE46K cross-seeded mWT alpha-synuclein fibril |
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要素 |
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-超分子 #1: the hE46K cross-seeded mWT alpha-synuclein fibril
超分子 | 名称: the hE46K cross-seeded mWT alpha-synuclein fibril / 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: ![]() ![]() |
組換発現 | 生物種: ![]() ![]() |
-分子 #1: Alpha-synuclein
分子 | 名称: Alpha-synuclein / タイプ: protein_or_peptide / ID: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() ![]() |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: MDVFMKGLSK AKEGVVAAAE KTKQGVAEAA GKTKEGVLYV GSKTKEGVVH GVTTVAEKTK EQVTNVGGA VVTGVTAVAQ KTVEGAGNIA AATGFVKKDQ MGKGEEGYPQ EGILEDMPVD P GSEAYEMP SEEGYQDYEP EA |
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
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![]() | らせん対称体再構成法 |
試料の集合状態 | filament |
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試料調製
緩衝液 | pH: 7.4 |
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凍結 | 凍結剤: ETHANE |
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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) 平均電子線量: 35.0 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: ![]() |
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 |