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基本情報
登録情報 | ![]() | |||||||||
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タイトル | Tau - CTE-MIA18 (tau intermediate amyloid) | |||||||||
![]() | Sharpened map | |||||||||
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![]() | Amyloid / tau / PROTEIN FIBRIL | |||||||||
機能・相同性 | ![]() plus-end-directed organelle transport along microtubule / axonal transport / histone-dependent DNA binding / neurofibrillary tangle assembly / positive regulation of diacylglycerol kinase activity / negative regulation of establishment of protein localization to mitochondrion / neurofibrillary tangle / positive regulation of protein localization to synapse / microtubule lateral binding / tubulin complex ...plus-end-directed organelle transport along microtubule / axonal transport / histone-dependent DNA binding / neurofibrillary tangle assembly / positive regulation of diacylglycerol kinase activity / negative regulation of establishment of protein localization to mitochondrion / neurofibrillary tangle / positive regulation of protein localization to synapse / microtubule lateral binding / tubulin complex / phosphatidylinositol bisphosphate binding / main axon / regulation of long-term synaptic depression / negative regulation of kinase activity / negative regulation of tubulin deacetylation / generation of neurons / regulation of chromosome organization / positive regulation of protein localization / rRNA metabolic process / internal protein amino acid acetylation / regulation of mitochondrial fission / intracellular distribution of mitochondria / axonal transport of mitochondrion / axon development / central nervous system neuron development / regulation of microtubule polymerization / microtubule polymerization / minor groove of adenine-thymine-rich DNA binding / lipoprotein particle binding / dynactin binding / apolipoprotein binding / glial cell projection / negative regulation of mitochondrial membrane potential / protein polymerization / negative regulation of mitochondrial fission / axolemma / Caspase-mediated cleavage of cytoskeletal proteins / regulation of microtubule polymerization or depolymerization / positive regulation of axon extension / regulation of microtubule cytoskeleton organization / Activation of AMPK downstream of NMDARs / supramolecular fiber organization / regulation of cellular response to heat / stress granule assembly / cytoplasmic microtubule organization / regulation of calcium-mediated signaling / axon cytoplasm / positive regulation of microtubule polymerization / somatodendritic compartment / cellular response to brain-derived neurotrophic factor stimulus / synapse assembly / phosphatidylinositol binding / nuclear periphery / cellular response to nerve growth factor stimulus / positive regulation of superoxide anion generation / protein phosphatase 2A binding / regulation of autophagy / astrocyte activation / response to lead ion / synapse organization / microglial cell activation / Hsp90 protein binding / regulation of synaptic plasticity / PKR-mediated signaling / protein homooligomerization / memory / cytoplasmic ribonucleoprotein granule / microtubule cytoskeleton organization / cellular response to reactive oxygen species / SH3 domain binding / activation of cysteine-type endopeptidase activity involved in apoptotic process / microtubule cytoskeleton / neuron projection development / cell-cell signaling / protein-macromolecule adaptor activity / actin binding / single-stranded DNA binding / cellular response to heat / protein-folding chaperone binding / cell body / growth cone / microtubule binding / double-stranded DNA binding / microtubule / amyloid fibril formation / sequence-specific DNA binding / dendritic spine / learning or memory / nuclear speck / neuron projection / membrane raft / axon / negative regulation of gene expression / neuronal cell body / DNA damage response / dendrite / protein kinase binding / enzyme binding / mitochondrion / DNA binding 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: 2.97 Å | |||||||||
![]() | Lovestam S / Li D / Scheres SHW / Goedert M | |||||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Disease-specific tau filaments assemble via polymorphic intermediates. 著者: Sofia Lövestam / David Li / Jane L Wagstaff / Abhay Kotecha / Dari Kimanius / Stephen H McLaughlin / Alexey G Murzin / Stefan M V Freund / Michel Goedert / Sjors H W Scheres / ![]() ![]() 要旨: Intermediate species in the assembly of amyloid filaments are believed to play a central role in neurodegenerative diseases and may constitute important targets for therapeutic intervention. However, ...Intermediate species in the assembly of amyloid filaments are believed to play a central role in neurodegenerative diseases and may constitute important targets for therapeutic intervention. However, structural information about intermediate species has been scarce and the molecular mechanisms by which amyloids assemble remain largely unknown. Here we use time-resolved cryogenic electron microscopy to study the in vitro assembly of recombinant truncated tau (amino acid residues 297-391) into paired helical filaments of Alzheimer's disease or into filaments of chronic traumatic encephalopathy. We report the formation of a shared first intermediate amyloid filament, with an ordered core comprising residues 302-316. Nuclear magnetic resonance indicates that the same residues adopt rigid, β-strand-like conformations in monomeric tau. At later time points, the first intermediate amyloid disappears and we observe many different intermediate amyloid filaments, with structures that depend on the reaction conditions. At the end of both assembly reactions, most intermediate amyloids disappear and filaments with the same ordered cores as those from human brains remain. Our results provide structural insights into the processes of primary and secondary nucleation of amyloid assembly, with implications for the design of new therapies. | |||||||||
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 | ![]() | 57.2 MB | ![]() | |
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ヘッダ (付随情報) | ![]() ![]() | 16.1 KB 16.1 KB | 表示 表示 | ![]() |
FSC (解像度算出) | ![]() | 13.6 KB | 表示 | ![]() |
画像 | ![]() | 27.5 KB | ||
Filedesc metadata | ![]() | 5.3 KB | ||
その他 | ![]() ![]() ![]() | 201.5 MB 172.1 MB 172.1 MB | ||
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-検証レポート
文書・要旨 | ![]() | 1 MB | 表示 | ![]() |
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文書・詳細版 | ![]() | 1 MB | 表示 | |
XML形式データ | ![]() | 21.4 KB | 表示 | |
CIF形式データ | ![]() | 28.2 KB | 表示 | |
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-関連構造データ
関連構造データ | ![]() 8q9eMC ![]() 8ppoC ![]() 8q27C ![]() 8q2jC ![]() 8q2kC ![]() 8q2lC ![]() 8q7fC ![]() 8q7lC ![]() 8q7mC ![]() 8q7pC ![]() 8q7tC ![]() 8q88C ![]() 8q8cC ![]() 8q8dC ![]() 8q8eC ![]() 8q8fC ![]() 8q8lC ![]() 8q8mC ![]() 8q8rC ![]() 8q8sC ![]() 8q8uC ![]() 8q8vC ![]() 8q8wC ![]() 8q8xC ![]() 8q8yC ![]() 8q8zC ![]() 8q97C ![]() 8q98C ![]() 8q99C ![]() 8q9aC ![]() 8q9bC ![]() 8q9cC ![]() 8q9dC ![]() 8q9fC ![]() 8q9gC ![]() 8q9hC ![]() 8q9iC ![]() 8q9jC ![]() 8q9kC ![]() 8q9lC ![]() 8q9mC ![]() 8q9oC ![]() 8qcpC ![]() 8qcrC ![]() 8qjjC 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 ( |
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類似構造データ | 類似検索 - 機能・相同性 ![]() |
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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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注釈 | Sharpened map | ||||||||||||||||||||
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
-追加マップ: Unsharpened map
ファイル | emd_18278_additional_1.map | ||||||||||||
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注釈 | Unsharpened map | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: Half map 1
ファイル | emd_18278_half_map_1.map | ||||||||||||
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注釈 | Half map 1 | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: Half map2
ファイル | emd_18278_half_map_2.map | ||||||||||||
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注釈 | Half map2 | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
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試料の構成要素
-全体 : Amyloid
全体 | 名称: Amyloid |
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要素 |
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-超分子 #1: Amyloid
超分子 | 名称: Amyloid / タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: all |
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由来(天然) | 生物種: ![]() |
-分子 #1: Isoform Tau-D of Microtubule-associated protein tau
分子 | 名称: Isoform Tau-D of Microtubule-associated protein tau / タイプ: protein_or_peptide / ID: 1 / コピー数: 6 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 40.002773 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: MAEPRQEFEV MEDHAGTYGL GDRKDQGGYT MHQDQEGDTD AGLKEEAGIG DTPSLEDEAA GHVTQARMVS KSKDGTGSDD KKAKGADGK TKIATPRGAA PPGQKGQANA TRIPAKTPPA PKTPPSSGEP PKSGDRSGYS SPGSPGTPGS RSRTPSLPTP P TREPKKVA ...文字列: MAEPRQEFEV MEDHAGTYGL GDRKDQGGYT MHQDQEGDTD AGLKEEAGIG DTPSLEDEAA GHVTQARMVS KSKDGTGSDD KKAKGADGK TKIATPRGAA PPGQKGQANA TRIPAKTPPA PKTPPSSGEP PKSGDRSGYS SPGSPGTPGS RSRTPSLPTP P TREPKKVA VVRTPPKSPS SAKSRLQTAP VPMPDLKNVK SKIGSTENLK HQPGGGKVQI INKKLDLSNV QSKCGSKDNI KH VPGGGSV QIVYKPVDLS KVTSKCGSLG NIHHKPGGGQ VEVKSEKLDF KDRVQSKIGS LDNITHVPGG GNKKIETHKL TFR ENAKAK TDHGAEIVYK SPVVSGDTSP RHLSNVSSTG SIDMVDSPQL ATLADEVSAS LAKQGL UniProtKB: Microtubule-associated protein tau |
-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: 7.2 |
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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: 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: ![]() |
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): 2.5 µm / 最小 デフォーカス(公称値): 0.5 µm |
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |