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データを開く
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基本情報
登録情報 | データベース: PDB / ID: 7ncg | |||||||||||||||
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タイトル | Type 2A alpha-synuclein filament seeded in vitro by filaments purified from Multiple Systems Atrophy Case 2 | |||||||||||||||
![]() | Alpha-synuclein | |||||||||||||||
![]() | PROTEIN FIBRIL / Amyloid / Multiple System Atrophy / Neurodegeneration / alpha-synuclein / filament | |||||||||||||||
機能・相同性 | ![]() negative regulation of mitochondrial electron transport, NADH to ubiquinone / : / neutral lipid metabolic process / regulation of acyl-CoA biosynthetic process / negative regulation of dopamine uptake involved in synaptic transmission / negative regulation of norepinephrine uptake / positive regulation of SNARE complex assembly / positive regulation of hydrogen peroxide catabolic process / supramolecular fiber / mitochondrial membrane organization ...negative regulation of mitochondrial electron transport, NADH to ubiquinone / : / neutral lipid metabolic process / regulation of acyl-CoA biosynthetic process / negative regulation of dopamine uptake involved in synaptic transmission / negative regulation of norepinephrine uptake / positive regulation of SNARE complex assembly / positive regulation of hydrogen peroxide catabolic process / supramolecular fiber / mitochondrial membrane organization / negative regulation of chaperone-mediated autophagy / regulation of synaptic vesicle recycling / regulation of reactive oxygen species biosynthetic process / 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 / response to iron(II) ion / SNARE complex assembly / positive regulation of neurotransmitter secretion / dopamine biosynthetic process / regulation of norepinephrine uptake / transporter regulator activity / regulation of locomotion / synaptic vesicle priming / mitochondrial ATP synthesis coupled electron transport / regulation of macrophage activation / positive regulation of inositol phosphate biosynthetic process / negative regulation of microtubule polymerization / synaptic vesicle transport / positive regulation of receptor recycling / dopamine uptake involved in synaptic transmission / protein kinase inhibitor activity / dynein complex binding / regulation of dopamine secretion / negative regulation of thrombin-activated receptor signaling pathway / cuprous ion binding / positive regulation of endocytosis / positive regulation of exocytosis / response to magnesium ion / synaptic vesicle exocytosis / enzyme inhibitor activity / kinesin binding / synaptic vesicle endocytosis / regulation of presynapse assembly / response to type II interferon / cysteine-type endopeptidase inhibitor activity / negative regulation of serotonin uptake / alpha-tubulin binding / supramolecular fiber organization / inclusion body / phospholipid metabolic process / cellular response to copper ion / axon terminus / cellular response to epinephrine stimulus / Hsp70 protein binding / response to interleukin-1 / regulation of microtubule cytoskeleton organization / SNARE binding / positive regulation of release of sequestered calcium ion into cytosol / adult locomotory behavior / negative regulation of protein kinase activity / excitatory postsynaptic potential / fatty acid metabolic process / phosphoprotein binding / protein tetramerization / microglial cell activation / regulation of long-term neuronal synaptic plasticity / synapse organization / ferrous iron binding / protein destabilization / PKR-mediated signaling / phospholipid binding / receptor internalization / tau protein binding / long-term synaptic potentiation / synaptic vesicle membrane / positive regulation of inflammatory response / actin cytoskeleton / actin binding / growth cone / cell cortex / cellular response to oxidative stress / neuron apoptotic process / chemical synaptic transmission / molecular adaptor activity / negative regulation of neuron apoptotic process / response to lipopolysaccharide / histone binding / amyloid fibril formation / lysosome / oxidoreductase activity / postsynapse / transcription cis-regulatory region binding / positive regulation of apoptotic process / Amyloid fiber formation / copper ion binding / response to xenobiotic stimulus / axon / neuronal cell body 類似検索 - 分子機能 | |||||||||||||||
生物種 | ![]() | |||||||||||||||
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: 3.43 Å | |||||||||||||||
![]() | Lovestam, S.K.A. / Schweighauser, M. / Scheres, S.H.W. | |||||||||||||||
資金援助 | ![]() ![]()
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![]() | ![]() タイトル: Seeded assembly in vitro does not replicate the structures of α-synuclein filaments from multiple system atrophy. 著者: Sofia Lövestam / Manuel Schweighauser / Tomoyasu Matsubara / Shigeo Murayama / Taisuke Tomita / Takashi Ando / Kazuko Hasegawa / Mari Yoshida / Airi Tarutani / Masato Hasegawa / Michel ...著者: Sofia Lövestam / Manuel Schweighauser / Tomoyasu Matsubara / Shigeo Murayama / Taisuke Tomita / Takashi Ando / Kazuko Hasegawa / Mari Yoshida / Airi Tarutani / Masato Hasegawa / Michel Goedert / Sjors H W Scheres / ![]() ![]() 要旨: The propagation of conformational strains by templated seeding is central to the prion concept. Seeded assembly of α-synuclein into filaments is believed to underlie the prion-like spreading of ...The propagation of conformational strains by templated seeding is central to the prion concept. Seeded assembly of α-synuclein into filaments is believed to underlie the prion-like spreading of protein inclusions in a number of human neurodegenerative diseases, including Parkinson's disease, dementia with Lewy bodies (DLB) and multiple system atrophy (MSA). We previously determined the atomic structures of α-synuclein filaments from the putamen of five individuals with MSA. Here, we used filament preparations from three of these brains for the in vitro seeded assembly of recombinant human α-synuclein. We find that the structures of the seeded assemblies differ from those of the seeds, suggesting that additional, as yet unknown, factors play a role in the propagation of the seeds. Identification of these factors will be essential for understanding the prion-like spreading of α-synuclein proteinopathies. | |||||||||||||||
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 | 分子: ![]() ![]() |
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ダウンロードとリンク
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ダウンロード
PDBx/mmCIF形式 | ![]() | 227.3 KB | 表示 | ![]() |
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PDB形式 | ![]() | 184 KB | 表示 | ![]() |
PDBx/mmJSON形式 | ![]() | ツリー表示 | ![]() | |
その他 | ![]() |
-検証レポート
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
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-関連構造データ
関連構造データ | ![]() 12265MC ![]() 7ncaC ![]() 7nchC ![]() 7nciC ![]() 7ncjC ![]() 7nckC M: このデータのモデリングに利用したマップデータ C: 同じ文献を引用 ( |
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類似構造データ | |
電子顕微鏡画像生データ | ![]() Data size: 1.1 TB Data #1: Unaligned movies of alpha-synuclein filament seeded in vitro by filaments purified from Multiple Systems Atrophy Case 1 [micrographs - multiframe] Data #2: Unaligned movies of alpha-synuclein filament seeded in vitro by filaments purified from Multiple Systems Atrophy Case 2 [micrographs - multiframe] Data #3: Unaligned movies of alpha-synuclein filament seeded in vitro by filaments purified from Multiple Systems Atrophy Case 5 [micrographs - multiframe] Data #4: Type 1A particles after Bayesian polishing [picked particles - single frame - processed] Data #5: Type 2A particles after Bayesian polishing [picked particles - single frame - processed] Data #6: Type 1B particles after Bayesian polishing [picked particles - single frame - processed] Data #7: Type 2B particles after Bayesian polishing [picked particles - single frame - processed] Data #8: Type 2AB particles after Bayesian polishing [picked particles - single frame - processed] Data #9: Type 3 particles after Bayesian polishing [picked particles - single frame - processed]) |
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リンク
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集合体
登録構造単位 | ![]()
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2 | ![]()
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要素
#1: タンパク質 | 分子量: 14476.108 Da / 分子数: 12 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() ![]() |
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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 |
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試料調製
構成要素 | 名称: Alpha synuclein filament / タイプ: COMPLEX / Entity ID: all / 由来: RECOMBINANT |
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分子量 | 実験値: NO |
由来(天然) | 生物種: ![]() |
由来(組換発現) | 生物種: ![]() ![]() |
緩衝液 | pH: 6.5 |
試料 | 濃度: 1 mg/ml / 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: 277 K / 詳細: LMB vitrobot IV |
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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: ![]() |
電子レンズ | モード: BRIGHT FIELD / 最大 デフォーカス(公称値): 3000 nm / 最小 デフォーカス(公称値): 1500 nm / Cs: 2.7 mm / C2レンズ絞り径: 50 µm / アライメント法: ZEMLIN TABLEAU |
試料ホルダ | 凍結剤: NITROGEN 試料ホルダーモデル: FEI TITAN KRIOS AUTOGRID HOLDER |
撮影 | 電子線照射量: 32.6 e/Å2 / 検出モード: COUNTING フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) |
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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: -0.95 ° / 軸方向距離/サブユニット: 4.75 Å / らせん対称軸の対称性: C2 | |||||||||||||||||||||||||
3次元再構成 | 解像度: 3.43 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 82474 / アルゴリズム: FOURIER SPACE / 対称性のタイプ: HELICAL |