+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-0077 | |||||||||||||||||||||
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タイトル | Narrow Pick Filament from Pick's disease brain | |||||||||||||||||||||
マップデータ | ||||||||||||||||||||||
試料 |
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キーワード | tau protein / tau / Pick's disease / tauopathy / neurodegenerative disease / proteinopathy / amyloid / filament / helical / Pick body / fibril / neurodegeneration / MAPT / microtubule-associated protein tau / PROTEIN FIBRIL | |||||||||||||||||||||
機能・相同性 | 機能・相同性情報 plus-end-directed organelle transport along microtubule / histone-dependent DNA binding / neurofibrillary tangle assembly / positive regulation of diacylglycerol kinase activity / axonal transport / 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 / histone-dependent DNA binding / neurofibrillary tangle assembly / positive regulation of diacylglycerol kinase activity / axonal transport / 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 / rRNA metabolic process / internal protein amino acid acetylation / regulation of chromosome organization / regulation of mitochondrial fission / axonal transport of mitochondrion / axon development / intracellular distribution of mitochondria / central nervous system neuron development / regulation of microtubule polymerization / microtubule polymerization / lipoprotein particle binding / minor groove of adenine-thymine-rich DNA binding / dynactin binding / glial cell projection / negative regulation of mitochondrial membrane potential / apolipoprotein binding / protein polymerization / axolemma / negative regulation of mitochondrial fission / 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 / positive regulation of protein localization / regulation of cellular response to heat / cytoplasmic microtubule organization / stress granule assembly / supramolecular fiber organization / regulation of calcium-mediated signaling / axon cytoplasm / somatodendritic compartment / positive regulation of microtubule polymerization / 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 / microglial cell activation / synapse organization / Hsp90 protein binding / protein homooligomerization / PKR-mediated signaling / regulation of synaptic plasticity / memory / activation of cysteine-type endopeptidase activity involved in apoptotic process / microtubule cytoskeleton organization / SH3 domain binding / cellular response to reactive oxygen species / cytoplasmic ribonucleoprotein granule / microtubule cytoskeleton / neuron projection development / cell-cell signaling / protein-macromolecule adaptor activity / protein-folding chaperone binding / single-stranded DNA binding / actin binding / cellular response to heat / cell body / growth cone / microtubule binding / double-stranded DNA binding / microtubule / sequence-specific DNA binding / amyloid fibril formation / dendritic spine / learning or memory / nuclear speck / neuron projection / membrane raft / axon / negative regulation of gene expression / neuronal cell body / dendrite / DNA damage response / protein kinase binding / enzyme binding / mitochondrion / DNA binding 類似検索 - 分子機能 | |||||||||||||||||||||
生物種 | Homo sapiens (ヒト) | |||||||||||||||||||||
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: 3.2 Å | |||||||||||||||||||||
データ登録者 | Falcon B / Zhang W | |||||||||||||||||||||
資金援助 | 英国, 米国, 6件
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引用 | ジャーナル: Nature / 年: 2018 タイトル: Structures of filaments from Pick's disease reveal a novel tau protein fold. 著者: Benjamin Falcon / Wenjuan Zhang / Alexey G Murzin / Garib Murshudov / Holly J Garringer / Ruben Vidal / R Anthony Crowther / Bernardino Ghetti / Sjors H W Scheres / Michel Goedert / 要旨: The ordered assembly of tau protein into abnormal filamentous inclusions underlies many human neurodegenerative diseases. Tau assemblies seem to spread through specific neural networks in each ...The ordered assembly of tau protein into abnormal filamentous inclusions underlies many human neurodegenerative diseases. Tau assemblies seem to spread through specific neural networks in each disease, with short filaments having the greatest seeding activity. The abundance of tau inclusions strongly correlates with disease symptoms. Six tau isoforms are expressed in the normal adult human brain-three isoforms with four microtubule-binding repeats each (4R tau) and three isoforms that lack the second repeat (3R tau). In various diseases, tau filaments can be composed of either 3R or 4R tau, or of both. Tau filaments have distinct cellular and neuroanatomical distributions, with morphological and biochemical differences suggesting that they may be able to adopt disease-specific molecular conformations. Such conformers may give rise to different neuropathological phenotypes, reminiscent of prion strains. However, the underlying structures are not known. Using electron cryo-microscopy, we recently reported the structures of tau filaments from patients with Alzheimer's disease, which contain both 3R and 4R tau. Here we determine the structures of tau filaments from patients with Pick's disease, a neurodegenerative disorder characterized by frontotemporal dementia. The filaments consist of residues Lys254-Phe378 of 3R tau, which are folded differently from the tau filaments in Alzheimer's disease, establishing the existence of conformers of assembled tau. The observed tau fold in the filaments of patients with Pick's disease explains the selective incorporation of 3R tau in Pick bodies, and the differences in phosphorylation relative to the tau filaments of Alzheimer's disease. Our findings show how tau can adopt distinct folds in the human brain in different diseases, an essential step for understanding the formation and propagation of molecular conformers. | |||||||||||||||||||||
履歴 |
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-構造の表示
構造ビューア | EMマップ: SurfViewMolmilJmol/JSmol |
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添付画像 |
-ダウンロードとリンク
-EMDBアーカイブ
マップデータ | emd_0077.map.gz | 201.8 KB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-0077-v30.xml emd-0077.xml | 17.4 KB 17.4 KB | 表示 表示 | EMDBヘッダ |
FSC (解像度算出) | emd_0077_fsc.xml | 9.6 KB | 表示 | FSCデータファイル |
画像 | emd_0077.png | 119.7 KB | ||
マスクデータ | emd_0077_msk_1.map | 75.1 MB | マスクマップ | |
Filedesc metadata | emd-0077.cif.gz | 5.6 KB | ||
その他 | emd_0077_half_map_1.map.gz emd_0077_half_map_2.map.gz | 58.4 MB 58.4 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-0077 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-0077 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_0077_validation.pdf.gz | 644.2 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_0077_full_validation.pdf.gz | 643.8 KB | 表示 | |
XML形式データ | emd_0077_validation.xml.gz | 16.5 KB | 表示 | |
CIF形式データ | emd_0077_validation.cif.gz | 21.7 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-0077 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-0077 | HTTPS FTP |
-関連構造データ
-リンク
EMDBのページ | EMDB (EBI/PDBe) / EMDataResource |
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「今月の分子」の関連する項目 |
-マップ
ファイル | ダウンロード / ファイル: emd_0077.map.gz / 形式: CCP4 / 大きさ: 75.1 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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投影像・断面図 | 画像のコントロール
画像は Spider により作成 | ||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 1.15 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
-マスク #1
ファイル | emd_0077_msk_1.map | ||||||||||||
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投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: #2
ファイル | emd_0077_half_map_1.map | ||||||||||||
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投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: #1
ファイル | emd_0077_half_map_2.map | ||||||||||||
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投影像・断面図 |
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密度ヒストグラム |
-試料の構成要素
-全体 : Tau filaments extracted from the frontotemporal cortex of a patie...
全体 | 名称: Tau filaments extracted from the frontotemporal cortex of a patient with Pick's disease |
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要素 |
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-超分子 #1: Tau filaments extracted from the frontotemporal cortex of a patie...
超分子 | 名称: Tau filaments extracted from the frontotemporal cortex of a patient with Pick's disease 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: Homo sapiens (ヒト) / 器官: Brain / 組織: Frontotemporal cortex |
-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: 3 / 光学異性体: LEVO |
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由来(天然) | 生物種: Homo sapiens (ヒト) / 器官: Brain / 組織: Frontotemporal cortex |
分子量 | 理論値: 10.135665 KDa |
配列 | 文字列: KNVKSKIGST ENLKHQPGGG KVQIVYKPVD LSKVTSKCGS LGNIHHKPGG GQVEVKSEKL DFKDRVQSKI GSLDNITHVP GGGNKKIET HKLTF 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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解析 | らせん対称体再構成法 |
試料の集合状態 | tissue |
-試料調製
濃度 | 0.5 mg/mL | ||||||||||||
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緩衝液 | pH: 7.4 構成要素:
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グリッド | モデル: Quantifoil R1.2/1.3 / 材質: GOLD / メッシュ: 300 / 前処理 - タイプ: GLOW DISCHARGE | ||||||||||||
凍結 | 凍結剤: ETHANE / チャンバー内湿度: 100 % / チャンバー内温度: 277 K / 装置: FEI VITROBOT MARK IV | ||||||||||||
詳細 | Dispersed filaments |
-電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
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特殊光学系 | エネルギーフィルター - 名称: GIF Quantum LS |
撮影 | フィルム・検出器のモデル: GATAN K2 QUANTUM (4k x 4k) 検出モード: COUNTING / 平均電子線量: 1.06 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: FIELD EMISSION GUN |
電子光学系 | 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELD / Cs: 2.7 mm 最大 デフォーカス(公称値): 2.8000000000000003 µm 最小 デフォーカス(公称値): 1.7 µm |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
-画像解析
-原子モデル構築 1
詳細 | Fourier-space refinement of the complete atomic model against the narrow Pick filament map was performed in REFMAC. A stack of three consecutive monomers was refined to preserve nearest-neighbour interactions for the middle chain. |
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精密化 | 空間: RECIPROCAL / プロトコル: AB INITIO MODEL / 温度因子: 57 / 当てはまり具合の基準: Fourier shell correlation |
得られたモデル | PDB-6gx5: |