+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-16188 | |||||||||||||||
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タイトル | Cryo-EM structure of alpha-synuclein singlet filament from Juvenile-onset synucleinopathy | |||||||||||||||
マップデータ | ||||||||||||||||
試料 |
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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 / negative regulation of chaperone-mediated autophagy / mitochondrial membrane organization / 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 / dopamine biosynthetic process / SNARE complex assembly / positive regulation of neurotransmitter secretion / synaptic vesicle priming / dopamine uptake involved in synaptic transmission / regulation of locomotion / positive regulation of inositol phosphate biosynthetic process / regulation of macrophage activation / mitochondrial ATP synthesis coupled electron transport / negative regulation of microtubule polymerization / 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 / positive regulation of endocytosis / cysteine-type endopeptidase inhibitor activity involved in apoptotic process / response to magnesium ion / kinesin binding / regulation of presynapse assembly / alpha-tubulin binding / synaptic vesicle endocytosis / negative regulation of serotonin uptake / localization / phospholipid metabolic process / supramolecular fiber organization / axon terminus / 封入体 / cellular response to copper ion / Hsp70 protein binding / cellular response to epinephrine stimulus / 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 / regulation of transmembrane transporter activity / ferrous iron binding / protein tetramerization / synapse organization / phosphoprotein binding / regulation of long-term neuronal synaptic plasticity / microglial cell activation / negative regulation of protein kinase activity / phospholipid binding / protein destabilization / PKR-mediated signaling / negative regulation of cysteine-type endopeptidase activity involved in apoptotic process / tau protein binding / positive regulation of protein serine/threonine kinase activity / receptor internalization / synaptic vesicle membrane / positive regulation of inflammatory response / activation of cysteine-type endopeptidase activity involved in apoptotic process / マイクロフィラメント / positive regulation of peptidyl-serine phosphorylation / cellular response to oxidative stress / actin binding / 細胞皮質 / 成長円錐 / histone binding / chemical synaptic transmission / postsynapse / neuron apoptotic process / negative regulation of neuron apoptotic process / amyloid fibril formation / response to lipopolysaccharide / リソソーム / oxidoreductase activity / molecular adaptor activity / transcription cis-regulatory region binding 類似検索 - 分子機能 | |||||||||||||||
生物種 | Homo sapiens (ヒト) / human (ヒト) / Human (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: 2.0 Å | |||||||||||||||
データ登録者 | Yang Y / Garringer JH / Shi Y / Lovestam S / Peak-Chew SY / Zhang XJ / Kotecha A / Bacioglu M / Koto A / Takao M ...Yang Y / Garringer JH / Shi Y / Lovestam S / Peak-Chew SY / Zhang XJ / Kotecha A / Bacioglu M / Koto A / Takao M / Spillantini GM / Ghetti B / Vidal R / Murzin GA / 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: Acta Neuropathol / 年: 2023 タイトル: New SNCA mutation and structures of α-synuclein filaments from juvenile-onset synucleinopathy. 著者: Yang Yang / Holly J Garringer / Yang Shi / Sofia Lövestam / Sew Peak-Chew / Xianjun Zhang / Abhay Kotecha / Mehtap Bacioglu / Atsuo Koto / Masaki Takao / Maria Grazia Spillantini / ...著者: Yang Yang / Holly J Garringer / Yang Shi / Sofia Lövestam / Sew Peak-Chew / Xianjun Zhang / Abhay Kotecha / Mehtap Bacioglu / Atsuo Koto / Masaki Takao / Maria Grazia Spillantini / Bernardino Ghetti / Ruben Vidal / Alexey G Murzin / Sjors H W Scheres / Michel Goedert / 要旨: A 21-nucleotide duplication in one allele of SNCA was identified in a previously described disease with abundant α-synuclein inclusions that we now call juvenile-onset synucleinopathy (JOS). This ...A 21-nucleotide duplication in one allele of SNCA was identified in a previously described disease with abundant α-synuclein inclusions that we now call juvenile-onset synucleinopathy (JOS). This mutation translates into the insertion of MAAAEKT after residue 22 of α-synuclein, resulting in a protein of 147 amino acids. Both wild-type and mutant proteins were present in sarkosyl-insoluble material that was extracted from frontal cortex of the individual with JOS and examined by electron cryo-microscopy. The structures of JOS filaments, comprising either a single protofilament, or a pair of protofilaments, revealed a new α-synuclein fold that differs from the folds of Lewy body diseases and multiple system atrophy (MSA). The JOS fold consists of a compact core, the sequence of which (residues 36-100 of wild-type α-synuclein) is unaffected by the mutation, and two disconnected density islands (A and B) of mixed sequences. There is a non-proteinaceous cofactor bound between the core and island A. The JOS fold resembles the common substructure of MSA Type I and Type II dimeric filaments, with its core segment approximating the C-terminal body of MSA protofilaments B and its islands mimicking the N-terminal arm of MSA protofilaments A. The partial similarity of JOS and MSA folds extends to the locations of their cofactor-binding sites. In vitro assembly of recombinant wild-type α-synuclein, its insertion mutant and their mixture yielded structures that were distinct from those of JOS filaments. Our findings provide insight into a possible mechanism of JOS fibrillation in which mutant α-synuclein of 147 amino acids forms a nucleus with the JOS fold, around which wild-type and mutant proteins assemble during elongation. | |||||||||||||||
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_16188.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-16188-v30.xml emd-16188.xml | 16.2 KB 16.2 KB | 表示 表示 | EMDBヘッダ |
FSC (解像度算出) | emd_16188_fsc.xml | 9.1 KB | 表示 | FSCデータファイル |
画像 | emd_16188.png | 46.1 KB | ||
マスクデータ | emd_16188_msk_1.map | 64 MB | マスクマップ | |
その他 | emd_16188_half_map_1.map.gz emd_16188_half_map_2.map.gz | 25.6 MB 25.6 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-16188 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-16188 | 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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-マップ
ファイル | ダウンロード / ファイル: emd_16188.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_16188_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_16188_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_16188_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 singlet filament extracted from the human brain w...
全体 | 名称: Alpha-synuclein singlet filament extracted from the human brain with JOS |
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要素 |
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-超分子 #1: Alpha-synuclein singlet filament extracted from the human brain w...
超分子 | 名称: Alpha-synuclein singlet filament extracted from the human brain with JOS タイプ: tissue / ID: 1 / 親要素: 0 / 含まれる分子: #1-#2 |
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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: human (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 |
-分子 #2: Unknown protein
分子 | 名称: Unknown protein / 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: Human (ヒト) |
分子量 | 理論値: 613.749 Da |
配列 | 文字列: (UNK)(UNK)(UNK)(UNK)(UNK)(UNK)(UNK) |
-分子 #3: water
分子 | 名称: water / タイプ: ligand / ID: 3 / コピー数: 8 / 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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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 FIELDBright-field microscopy 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 |
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 |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
-画像解析
-原子モデル構築 1
詳細 | servalcat |
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得られたモデル | PDB-8bqv: |