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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: 6nwq | |||||||||||||||||||||
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タイトル | Chronic traumatic encephalopathy Type II Tau filament | |||||||||||||||||||||
![]() | Microtubule-associated protein tau | |||||||||||||||||||||
![]() | PROTEIN FIBRIL / Tau / chronic traumatic encephalopathy / filament / amyloid | |||||||||||||||||||||
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 | 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: 3.4 Å | |||||||||||||||||||||
![]() | Falcon, B. / Zivanov, J. / Zhang, W. / Murzin, A.G. / Garringer, H.J. / Vidal, R. / Crowther, R.A. / Newell, K.L. / Ghetti, B. / Goedert, M. / Scheres, H.W. | |||||||||||||||||||||
資金援助 | ![]() ![]()
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![]() | ![]() タイトル: Novel tau filament fold in chronic traumatic encephalopathy encloses hydrophobic molecules. 著者: Benjamin Falcon / Jasenko Zivanov / Wenjuan Zhang / Alexey G Murzin / Holly J Garringer / Ruben Vidal / R Anthony Crowther / Kathy L Newell / Bernardino Ghetti / Michel Goedert / Sjors H W Scheres / ![]() ![]() 要旨: Chronic traumatic encephalopathy (CTE) is a neurodegenerative tauopathy that is associated with repetitive head impacts or exposure to blast waves. First described as punch-drunk syndrome and ...Chronic traumatic encephalopathy (CTE) is a neurodegenerative tauopathy that is associated with repetitive head impacts or exposure to blast waves. First described as punch-drunk syndrome and dementia pugilistica in retired boxers, CTE has since been identified in former participants of other contact sports, ex-military personnel and after physical abuse. No disease-modifying therapies currently exist, and diagnosis requires an autopsy. CTE is defined by an abundance of hyperphosphorylated tau protein in neurons, astrocytes and cell processes around blood vessels. This, together with the accumulation of tau inclusions in cortical layers II and III, distinguishes CTE from Alzheimer's disease and other tauopathies. However, the morphologies of tau filaments in CTE and the mechanisms by which brain trauma can lead to their formation are unknown. Here we determine the structures of tau filaments from the brains of three individuals with CTE at resolutions down to 2.3 Å, using cryo-electron microscopy. We show that filament structures are identical in the three cases but are distinct from those of Alzheimer's and Pick's diseases, and from those formed in vitro. Similar to Alzheimer's disease, all six brain tau isoforms assemble into filaments in CTE, and residues K274-R379 of three-repeat tau and S305-R379 of four-repeat tau form the ordered core of two identical C-shaped protofilaments. However, a different conformation of the β-helix region creates a hydrophobic cavity that is absent in tau filaments from the brains of patients with Alzheimer's disease. This cavity encloses an additional density that is not connected to tau, which suggests that the incorporation of cofactors may have a role in tau aggregation in CTE. Moreover, filaments in CTE have distinct protofilament interfaces to those of Alzheimer's disease. Our structures provide a unifying neuropathological criterion for CTE, and support the hypothesis that the formation and propagation of distinct conformers of assembled tau underlie different neurodegenerative diseases. | |||||||||||||||||||||
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 | ![]() | 123.8 KB | 表示 | ![]() |
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PDB形式 | ![]() | 82 KB | 表示 | ![]() |
PDBx/mmJSON形式 | ![]() | ツリー表示 | ![]() | |
その他 | ![]() |
-検証レポート
文書・要旨 | ![]() | 1.2 MB | 表示 | ![]() |
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文書・詳細版 | ![]() | 1.2 MB | 表示 | |
XML形式データ | ![]() | 27.7 KB | 表示 | |
CIF形式データ | ![]() | 38 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 | ![]() 0528MC ![]() 0527C ![]() 6nwpC C: 同じ文献を引用 ( M: このデータのモデリングに利用したマップデータ |
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類似構造データ | |
電子顕微鏡画像生データ | ![]() Data size: 9.7 TB / Data #1: Raw Movies [micrographs - multiframe] / Data #2: Aligned Micrographs [micrographs - single frame]) |
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リンク
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集合体
登録構造単位 | ![]()
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要素
#1: タンパク質 | 分子量: 45919.871 Da / 分子数: 6 / 由来タイプ: 天然 / 由来: (天然) ![]() |
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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: TISSUE / 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: Tau filaments extracted from the temporal cortex of a patient with chronic traumatic encephalopathy タイプ: TISSUE / Entity ID: all / 由来: NATURAL | ||||||||||||
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由来(天然) | 生物種: ![]() | ||||||||||||
緩衝液 | pH: 7.4 | ||||||||||||
緩衝液成分 |
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試料 | 濃度: 0.5 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: 277.15 K |
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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 / 倍率(公称値): 130000 X / 最大 デフォーカス(公称値): 2800 nm / 最小 デフォーカス(公称値): 1700 nm / Cs: 2.7 mm |
撮影 | 平均露光時間: 9 sec. / 電子線照射量: 55.48 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) |
電子光学装置 | エネルギーフィルター名称: GIF Quantum LS / エネルギーフィルタースリット幅: 25 eV |
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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: 179.4 ° / 軸方向距離/サブユニット: 2.37 Å / らせん対称軸の対称性: C2 | ||||||||||||||||||||
3次元再構成 | 解像度: 3.4 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 7621 / 対称性のタイプ: HELICAL | ||||||||||||||||||||
原子モデル構築 | B value: 51.7 / 空間: RECIPROCAL / Target criteria: Fourier shell correlation 詳細: Fourier-space refinement of the complete atomic model against the chronic traumatic encephalopathy Type II Tau filament map was performed in REFMAC. A stack of three consecutive monomers was ...詳細: Fourier-space refinement of the complete atomic model against the chronic traumatic encephalopathy Type II Tau filament map was performed in REFMAC. A stack of three consecutive monomers was refined to preserve nearest-neighbour interactions for the middle chain. |