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基本情報
登録情報 | データベース: EMDB / ID: EMD-21200 | |||||||||
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タイトル | Doublet Tau Fibril from Corticobasal Degeneration Human Brain Tissue | |||||||||
![]() | Doublet Tau Fibril from Corticobasal Degeneration Human Brain Tissue | |||||||||
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![]() | Pathological amyloid fibril / cross-beta fold / parallel beta-sheets / 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 / cellular response to reactive oxygen species / SH3 domain binding / microtubule cytoskeleton organization / activation of cysteine-type endopeptidase activity involved in apoptotic process / neuron projection development / microtubule cytoskeleton / 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: 3.8 Å | |||||||||
![]() | Arakhamia T / Lee CE | |||||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Posttranslational Modifications Mediate the Structural Diversity of Tauopathy Strains. 著者: Tamta Arakhamia / Christina E Lee / Yari Carlomagno / Duc M Duong / Sean R Kundinger / Kevin Wang / Dewight Williams / Michael DeTure / Dennis W Dickson / Casey N Cook / Nicholas T Seyfried / ...著者: Tamta Arakhamia / Christina E Lee / Yari Carlomagno / Duc M Duong / Sean R Kundinger / Kevin Wang / Dewight Williams / Michael DeTure / Dennis W Dickson / Casey N Cook / Nicholas T Seyfried / Leonard Petrucelli / Anthony W P Fitzpatrick / ![]() 要旨: Tau aggregation into insoluble filaments is the defining pathological hallmark of tauopathies. However, it is not known what controls the formation and templated seeding of strain-specific structures ...Tau aggregation into insoluble filaments is the defining pathological hallmark of tauopathies. However, it is not known what controls the formation and templated seeding of strain-specific structures associated with individual tauopathies. Here, we use cryo-electron microscopy (cryo-EM) to determine the structures of tau filaments from corticobasal degeneration (CBD) human brain tissue. Cryo-EM and mass spectrometry of tau filaments from CBD reveal that this conformer is heavily decorated with posttranslational modifications (PTMs), enabling us to map PTMs directly onto the structures. By comparing the structures and PTMs of tau filaments from CBD and Alzheimer's disease, it is found that ubiquitination of tau can mediate inter-protofilament interfaces. We propose a structure-based model in which cross-talk between PTMs influences tau filament structure, contributing to the structural diversity of tauopathy strains. Our approach establishes a framework for further elucidating the relationship between the structures of polymorphic fibrils, including their PTMs, and neurodegenerative disease. | |||||||||
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 | EMマップ: ![]() ![]() ![]() |
添付画像 |
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マップデータ | ![]() | 1.1 MB | ![]() | |
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ヘッダ (付随情報) | ![]() ![]() | 9.6 KB 9.6 KB | 表示 表示 | ![]() |
画像 | ![]() | 266.1 KB | ||
Filedesc metadata | ![]() | 4.9 KB | ||
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-検証レポート
文書・要旨 | ![]() | 306.5 KB | 表示 | ![]() |
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文書・詳細版 | ![]() | 306 KB | 表示 | |
XML形式データ | ![]() | 6.1 KB | 表示 | |
CIF形式データ | ![]() | 6.9 KB | 表示 | |
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-関連構造データ
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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 | Doublet Tau Fibril from Corticobasal Degeneration Human Brain Tissue | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 1.414 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
CCP4マップ ヘッダ情報:
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-添付データ
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試料の構成要素
-全体 : Doublet Tau Fibril from Corticobasal Degeneration Human Brain Tissue
全体 | 名称: Doublet Tau Fibril from Corticobasal Degeneration Human Brain Tissue |
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要素 |
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-超分子 #1: Doublet Tau Fibril from Corticobasal Degeneration Human Brain Tissue
超分子 | 名称: Doublet Tau Fibril from Corticobasal Degeneration Human Brain Tissue タイプ: tissue / 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: Microtubule-associated protein tau
分子 | 名称: 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: 11.608375 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: KVQIINKKLD LSNVQSKCGS KDNIKHVPGG GSVQIVYKPV DLSKVTSKCG SLGNIHHKPG GGQVEVKSEK LDFKDRVQSK IGSLDNITH VPGGGNKKIE THKLTFRE 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: 7.4 |
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グリッド | 詳細: unspecified |
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: GATAN K2 SUMMIT (4k x 4k) 平均電子線量: 60.0 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 |
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |
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画像解析
最終 再構成 | 想定した対称性 - らせんパラメータ - Δz: 4.8 Å 想定した対称性 - らせんパラメータ - ΔΦ: -0.6 ° 想定した対称性 - らせんパラメータ - 軸対称性: C2 (2回回転対称) 解像度のタイプ: BY AUTHOR / 解像度: 3.8 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 7549 |
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初期モデル | モデルのタイプ: NONE |
最終 角度割当 | タイプ: NOT APPLICABLE |