+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-15285 | |||||||||||||||
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タイトル | Cryo-EM structure of alpha-synuclein filaments from Parkinson's disease and dementia with Lewy bodies | |||||||||||||||
マップデータ | ||||||||||||||||
試料 |
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キーワード | alpha-synuclein / amyloid / fibril / Parkinson's disease (PD) / Parkinson's disease dementia (PDD) / dementia with Lewy bodies (DLB) / synucleinopathy / 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 / 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 | らせん対称体再構成法 / クライオ電子顕微鏡法 / 解像度: 2.2 Å | |||||||||||||||
データ登録者 | Yang Y / Shi Y / Schweighauser M / Zhang XJ / Kotecha A / Murzin AG / Garringer HJ / Cullinane P / Saito Y / Foroud T ...Yang Y / Shi Y / Schweighauser M / Zhang XJ / Kotecha A / Murzin AG / Garringer HJ / Cullinane P / Saito Y / Foroud T / Warner TT / Hasegawa K / Vidal R / Murayama S / Revesz T / Ghetti B / Hasegawa M / Lashley T / Scheres HWS / Goedert M | |||||||||||||||
資金援助 | 英国, 米国, 4件
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引用 | ジャーナル: Nature / 年: 2022 タイトル: Structures of α-synuclein filaments from human brains with Lewy pathology. 著者: Yang Yang / Yang Shi / Manuel Schweighauser / Xianjun Zhang / Abhay Kotecha / Alexey G Murzin / Holly J Garringer / Patrick W Cullinane / Yuko Saito / Tatiana Foroud / Thomas T Warner / ...著者: Yang Yang / Yang Shi / Manuel Schweighauser / Xianjun Zhang / Abhay Kotecha / Alexey G Murzin / Holly J Garringer / Patrick W Cullinane / Yuko Saito / Tatiana Foroud / Thomas T Warner / Kazuko Hasegawa / Ruben Vidal / Shigeo Murayama / Tamas Revesz / Bernardino Ghetti / Masato Hasegawa / Tammaryn Lashley / Sjors H W Scheres / Michel Goedert / 要旨: Parkinson's disease (PD) is the most common movement disorder, with resting tremor, rigidity, bradykinesia and postural instability being major symptoms. Neuropathologically, it is characterized by ...Parkinson's disease (PD) is the most common movement disorder, with resting tremor, rigidity, bradykinesia and postural instability being major symptoms. Neuropathologically, it is characterized by the presence of abundant filamentous inclusions of α-synuclein in the form of Lewy bodies and Lewy neurites in some brain cells, including dopaminergic nerve cells of the substantia nigra. PD is increasingly recognised as a multisystem disorder, with cognitive decline being one of its most common non-motor symptoms. Many patients with PD develop dementia more than 10 years after diagnosis. PD dementia (PDD) is clinically and neuropathologically similar to dementia with Lewy bodies (DLB), which is diagnosed when cognitive impairment precedes parkinsonian motor signs or begins within one year from their onset. In PDD, cognitive impairment develops in the setting of well-established PD. Besides PD and DLB, multiple system atrophy (MSA) is the third major synucleinopathy. It is characterized by the presence of abundant filamentous α-synuclein inclusions in brain cells, especially oligodendrocytes (Papp-Lantos bodies). We previously reported the electron cryo-microscopy structures of two types of α-synuclein filament extracted from the brains of individuals with MSA. Each filament type is made of two different protofilaments. Here we report that the cryo-electron microscopy structures of α-synuclein filaments from the brains of individuals with PD, PDD and DLB are made of a single protofilament (Lewy fold) that is markedly different from the protofilaments of MSA. These findings establish the existence of distinct molecular conformers of assembled α-synuclein in neurodegenerative disease. | |||||||||||||||
履歴 |
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-構造の表示
添付画像 |
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-ダウンロードとリンク
-EMDBアーカイブ
マップデータ | emd_15285.map.gz | 25.6 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-15285-v30.xml emd-15285.xml | 17.5 KB 17.5 KB | 表示 表示 | EMDBヘッダ |
FSC (解像度算出) | emd_15285_fsc.xml | 9.1 KB | 表示 | FSCデータファイル |
画像 | emd_15285.png | 91.6 KB | ||
マスクデータ | emd_15285_msk_1.map | 64 MB | マスクマップ | |
Filedesc metadata | emd-15285.cif.gz | 5.4 KB | ||
その他 | emd_15285_half_map_1.map.gz emd_15285_half_map_2.map.gz | 25.5 MB 25.5 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-15285 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-15285 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_15285_validation.pdf.gz | 912.4 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_15285_full_validation.pdf.gz | 911.9 KB | 表示 | |
XML形式データ | emd_15285_validation.xml.gz | 16.3 KB | 表示 | |
CIF形式データ | emd_15285_validation.cif.gz | 21.4 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-15285 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-15285 | HTTPS FTP |
-関連構造データ
関連構造データ | 8a9lMC M: このマップから作成された原子モデル C: 同じ文献を引用 (文献) |
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類似構造データ | 類似検索 - 機能・相同性F&H 検索 |
-リンク
EMDBのページ | EMDB (EBI/PDBe) / EMDataResource |
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-マップ
ファイル | ダウンロード / ファイル: emd_15285.map.gz / 形式: CCP4 / 大きさ: 64 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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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: 0.727 Å | ||||||||||||||||||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
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-添付データ
-マスク #1
ファイル | emd_15285_msk_1.map | ||||||||||||
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投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: #2
ファイル | emd_15285_half_map_1.map | ||||||||||||
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投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: #1
ファイル | emd_15285_half_map_2.map | ||||||||||||
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投影像・断面図 |
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密度ヒストグラム |
-試料の構成要素
-全体 : Alpha-synuclein filaments extracted from the human brain with PD,...
全体 | 名称: Alpha-synuclein filaments extracted from the human brain with PD, PDD, and DLB |
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要素 |
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-超分子 #1: Alpha-synuclein filaments extracted from the human brain with PD,...
超分子 | 名称: Alpha-synuclein filaments extracted from the human brain with PD, PDD, and DLB タイプ: tissue / ID: 1 / 親要素: 0 / 含まれる分子: #1-#3 |
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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: 1 / 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 |
配列 | 文字列: MDVFMKGLSK AKEGVVAAAE KTKQGVAEAA GKTKEGVLYV GSKTKEGVVH GVATVAEKTK EQVTNVGGAV VTGVTAVAQK TVEGAGSIA AATGFVKKDQ LGKNEEGAPQ EGILEDMPVD PDNEAYEMPS EEGYQDYEPE A UniProtKB: Alpha-synuclein |
-分子 #2: Unknown fragment
分子 | 名称: Unknown fragment / タイプ: protein_or_peptide / ID: 2 / コピー数: 1 / 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: 783.958 Da |
配列 | 文字列: (UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK) |
-分子 #3: Unknown fragment
分子 | 名称: Unknown fragment / タイプ: protein_or_peptide / ID: 3 / コピー数: 1 / 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: 627.775 Da |
配列 | 文字列: (UNK)(UNK)(UNK)(UNK)V(UNK)(UNK) |
-分子 #4: water
分子 | 名称: water / タイプ: ligand / ID: 4 / コピー数: 6 / 式: HOH |
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分子量 | 理論値: 18.015 Da |
Chemical component information | ChemComp-HOH: |
-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: 7.5 |
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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: FEI FALCON IV (4k x 4k) 平均電子線量: 40.0 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 最大 デフォーカス(公称値): 1.4000000000000001 µm 最小 デフォーカス(公称値): 0.6 µm |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |