+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 6l4s | ||||||
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タイトル | cryo-em structure of alpha-synuclein fiber mutation type E46K | ||||||
要素 | Alpha-synucleinΑ-シヌクレイン | ||||||
キーワード | PROTEIN FIBRIL / alpha-syn fiber / Parkinson disease (パーキンソン病) | ||||||
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 / dopamine biosynthetic process / SNARE complex assembly / positive regulation of neurotransmitter secretion / regulation of locomotion / positive regulation of inositol phosphate biosynthetic process / synaptic vesicle priming / regulation of macrophage activation / dopamine uptake involved in synaptic transmission / 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 / mitochondrial ATP synthesis coupled electron transport / 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 / alpha-tubulin binding / negative regulation of serotonin uptake / localization / phospholipid metabolic process / axon terminus / supramolecular fiber organization / 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 / phosphoprotein binding / protein tetramerization / synapse organization / regulation of long-term neuronal synaptic plasticity / microglial cell activation / negative regulation of protein kinase activity / ferrous iron 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 / phospholipid binding / 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 / actin binding / cellular response to oxidative stress / 細胞皮質 / histone binding / 成長円錐 / postsynapse / chemical synaptic transmission / neuron apoptotic process / negative regulation of neuron apoptotic process / response to lipopolysaccharide / amyloid fibril formation / リソソーム / molecular adaptor activity / oxidoreductase activity / transcription cis-regulatory region binding 類似検索 - 分子機能 | ||||||
生物種 | Homo sapiens (ヒト) | ||||||
手法 | 電子顕微鏡法 / らせん対称体再構成法 / クライオ電子顕微鏡法 / 解像度: 3.37 Å | ||||||
データ登録者 | Li, Y.W. / Zhao, K. / Liu, C. / Li, X. | ||||||
引用 | ジャーナル: Nat Commun / 年: 2020 タイトル: Parkinson's disease associated mutation E46K of α-synuclein triggers the formation of a distinct fibril structure. 著者: Kun Zhao / Yaowang Li / Zhenying Liu / Houfang Long / Chunyu Zhao / Feng Luo / Yunpeng Sun / Youqi Tao / Xiao-Dong Su / Dan Li / Xueming Li / Cong Liu / 要旨: Amyloid aggregation of α-synuclein (α-syn) is closely associated with Parkinson's disease (PD) and other synucleinopathies. Several single amino-acid mutations (e.g. E46K) of α-syn have been ...Amyloid aggregation of α-synuclein (α-syn) is closely associated with Parkinson's disease (PD) and other synucleinopathies. Several single amino-acid mutations (e.g. E46K) of α-syn have been identified causative to the early onset of familial PD. Here, we report the cryo-EM structure of an α-syn fibril formed by N-terminally acetylated E46K mutant α-syn (Ac-E46K). The fibril structure represents a distinct fold of α-syn, which demonstrates that the E46K mutation breaks the electrostatic interactions in the wild type (WT) α-syn fibril and thus triggers the rearrangement of the overall structure. Furthermore, we show that the Ac-E46K fibril is less resistant to harsh conditions and protease cleavage, and more prone to be fragmented with an enhanced seeding capability than that of the WT fibril. Our work provides a structural view to the severe pathology of the PD familial mutation E46K of α-syn and highlights the importance of electrostatic interactions in defining the fibril polymorphs. | ||||||
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 | 分子: MolmilJmol/JSmol |
-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 6l4s.cif.gz | 57.3 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb6l4s.ent.gz | 43.8 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 6l4s.json.gz | ツリー表示 | PDBx/mmJSON形式 | |
その他 | その他のダウンロード |
-検証レポート
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/l4/6l4s ftp://data.pdbj.org/pub/pdb/validation_reports/l4/6l4s | HTTPS FTP |
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-関連構造データ
-リンク
-集合体
登録構造単位 |
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-要素
#1: タンパク質 | 分子量: 5402.157 Da / 分子数: 6 / 変異: E46K / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: SNCA, NACP, PARK1 / 発現宿主: Escherichia coli K-12 (大腸菌) / 株 (発現宿主): K-12 / 参照: UniProt: P37840 |
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-実験情報
-実験
実験 | 手法: 電子顕微鏡法 |
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EM実験 | 試料の集合状態: FILAMENT / 3次元再構成法: らせん対称体再構成法 |
-試料調製
構成要素 | 名称: alpha-synuclein fiber mutation type E46K / タイプ: COMPLEX / Entity ID: all / 由来: RECOMBINANT |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
由来(組換発現) | 生物種: Escherichia coli K-12 (大腸菌) / 株: K-12 |
緩衝液 | pH: 7.5 |
試料 | 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES |
急速凍結 | 装置: FEI VITROBOT MARK IV / 凍結剤: ETHANE / 湿度: 100 % / 凍結前の試料温度: 289 K |
-電子顕微鏡撮影
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
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顕微鏡 | モデル: FEI TITAN KRIOS |
電子銃 | 電子線源: FIELD EMISSION GUN / 加速電圧: 300 kV / 照射モード: FLOOD BEAM |
電子レンズ | モード: BRIGHT FIELDBright-field microscopy |
撮影 | 平均露光時間: 8 sec. / 電子線照射量: 50 e/Å2 / 検出モード: SUPER-RESOLUTION フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) |
画像スキャン | 動画フレーム数/画像: 32 / 利用したフレーム数/画像: 1-32 |
-解析
EMソフトウェア |
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CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||
らせん対称 | 回転角度/サブユニット: 179.371 ° / 軸方向距離/サブユニット: 2.376 Å / らせん対称軸の対称性: C1 | ||||||||||||||||
3次元再構成 | 解像度: 3.37 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 18009 / 対称性のタイプ: HELICAL |