+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-41610 | ||||||||||||
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タイトル | AT8-Phosphomimetic Tau Filaments (Full-length, Cofactor-Free 0N4R Tau S202E, T205E, S208E) | ||||||||||||
マップデータ | |||||||||||||
試料 |
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キーワード | Tau / Amyloid Fibril / Phosphomimetic / 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 / negative regulation of kinase activity / regulation of long-term synaptic depression / 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 / intracellular distribution of mitochondria / axon development / central nervous system neuron development / regulation of microtubule polymerization / apolipoprotein binding / microtubule polymerization / lipoprotein particle binding / minor groove of adenine-thymine-rich DNA binding / dynactin binding / glial cell projection / negative regulation of mitochondrial membrane potential / 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 / regulation of cellular response to heat / positive regulation of protein localization / cytoplasmic microtubule organization / stress granule assembly / supramolecular fiber organization / regulation of calcium-mediated signaling / axon cytoplasm / somatodendritic compartment / positive regulation of microtubule polymerization / synapse assembly / cellular response to brain-derived neurotrophic factor stimulus / 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 / SH3 domain binding / microtubule cytoskeleton organization / cytoplasmic ribonucleoprotein granule / cellular response to reactive oxygen species / microtubule cytoskeleton / neuron projection development / cell-cell signaling / single-stranded DNA binding / protein-folding chaperone binding / actin binding / protein-macromolecule adaptor activity / cellular response to heat / double-stranded DNA binding / growth cone / cell body / microtubule 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 / DNA damage response / dendrite / 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: 2.6 Å | ||||||||||||
データ登録者 | El Mammeri N / Dregni AJ / Duan P / Hong M | ||||||||||||
資金援助 | 米国, 3件
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引用 | ジャーナル: Proc Natl Acad Sci U S A / 年: 2024 タイトル: Structures of AT8 and PHF1 phosphomimetic tau: Insights into the posttranslational modification code of tau aggregation. 著者: Nadia El Mammeri / Aurelio J Dregni / Pu Duan / Mei Hong / 要旨: The microtubule-associated protein tau aggregates into amyloid fibrils in Alzheimer's disease and other neurodegenerative diseases. In these tauopathies, tau is hyperphosphorylated, suggesting that ...The microtubule-associated protein tau aggregates into amyloid fibrils in Alzheimer's disease and other neurodegenerative diseases. In these tauopathies, tau is hyperphosphorylated, suggesting that this posttranslational modification (PTM) may induce tau aggregation. Tau is also phosphorylated in normal developing brains. To investigate how tau phosphorylation induces amyloid fibrils, here we report the atomic structures of two phosphomimetic full-length tau fibrils assembled without anionic cofactors. We mutated key Ser and Thr residues to Glu in two regions of the protein. One construct contains three Glu mutations at the epitope of the anti-phospho-tau antibody AT8 (AT8-3E tau), whereas the other construct contains four Glu mutations at the epitope of the antibody PHF1 (PHF1-4E tau). Solid-state NMR data show that both phosphomimetic tau mutants form homogeneous fibrils with a single set of chemical shifts. The AT8-3E tau rigid core extends from the R3 repeat to the C terminus, whereas the PHF1-4E tau rigid core spans R2, R3, and R4 repeats. Cryoelectron microscopy data show that AT8-3E tau forms a triangular multi-layered core, whereas PHF1-4E tau forms a triple-stranded core. Interestingly, a construct combining all seven Glu mutations exhibits the same conformation as PHF1-4E tau. Scalar-coupled NMR data additionally reveal the dynamics and shape of the fuzzy coat surrounding the rigid cores. These results demonstrate that specific PTMs induce structurally specific tau aggregates, and the phosphorylation code of tau contains redundancy. | ||||||||||||
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 | emd_41610.map.gz | 54.1 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-41610-v30.xml emd-41610.xml | 18.7 KB 18.7 KB | 表示 表示 | EMDBヘッダ |
FSC (解像度算出) | emd_41610_fsc.xml | 18.1 KB | 表示 | FSCデータファイル |
画像 | emd_41610.png | 96.4 KB | ||
マスクデータ | emd_41610_msk_1.map | 512 MB | マスクマップ | |
Filedesc metadata | emd-41610.cif.gz | 6 KB | ||
その他 | emd_41610_additional_1.map.gz emd_41610_half_map_1.map.gz emd_41610_half_map_2.map.gz | 480 MB 410.5 MB 410.6 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-41610 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-41610 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_41610_validation.pdf.gz | 916.3 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_41610_full_validation.pdf.gz | 915.9 KB | 表示 | |
XML形式データ | emd_41610_validation.xml.gz | 26.2 KB | 表示 | |
CIF形式データ | emd_41610_validation.cif.gz | 34.8 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-41610 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-41610 | HTTPS FTP |
-関連構造データ
関連構造データ | 8ttlMC 8ttnC 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 (文献) |
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類似構造データ | 類似検索 - 機能・相同性F&H 検索 |
-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_41610.map.gz / 形式: CCP4 / 大きさ: 512 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: 0.8175 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_41610_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 |
-追加マップ: Unmasked final map
ファイル | emd_41610_additional_1.map | ||||||||||||
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注釈 | Unmasked final 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: #1
ファイル | emd_41610_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: #2
ファイル | emd_41610_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 : AT8-Phosphomimetic 0N4R Tau Fibrils
全体 | 名称: AT8-Phosphomimetic 0N4R Tau Fibrils |
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要素 |
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-超分子 #1: AT8-Phosphomimetic 0N4R Tau Fibrils
超分子 | 名称: AT8-Phosphomimetic 0N4R Tau Fibrils / 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: Homo sapiens (ヒト) |
-分子 #1: Microtubule-associated protein tau
分子 | 名称: Microtubule-associated protein tau / タイプ: protein_or_peptide / ID: 1 / 詳細: Using numbering from 2N4R Tau / コピー数: 6 / 光学異性体: LEVO |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 40.185934 KDa |
組換発現 | 生物種: Escherichia coli (大腸菌) |
配列 | 文字列: MAEPRQEFEV MEDHAGTYGL GDRKDQGGYT MHQDQEGDTD AGLKAEEAGI GDTPSLEDEA AGHVTQARMV SKSKDGTGSD DKKAKGADG KTKIATPRGA APPGQKGQAN ATRIPAKTPP APKTPPSSGE PPKSGDRSGY SSPGEPGEPG ERSRTPSLPT P PTREPKKV ...文字列: MAEPRQEFEV MEDHAGTYGL GDRKDQGGYT MHQDQEGDTD AGLKAEEAGI GDTPSLEDEA AGHVTQARMV SKSKDGTGSD DKKAKGADG KTKIATPRGA APPGQKGQAN ATRIPAKTPP APKTPPSSGE PPKSGDRSGY SSPGEPGEPG ERSRTPSLPT P PTREPKKV AVVRTPPKSP SSAKSRLQTA PVPMPDLKNV KSKIGSTENL KHQPGGGKVQ IINKKLDLSN VQSKCGSKDN IK HVPGGGS VQIVYKPVDL SKVTSKCGSL GNIHHKPGGG QVEVKSEKLD FKDRVQSKIG SLDNITHVPG GGNKKIETHK LTF RENAKA KTDHGAEIVY KSPVVSGDTS PRHLSNVSST GSIDMVDSPQ LATLADEVSA SLAKQGL 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 | filament |
-試料調製
濃度 | 0.4 mg/mL | ||||||||||||
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緩衝液 | pH: 6.8 構成要素:
詳細: 50 mM K2HPO4 buffer, pH 6.8, containing 300 mM NaCl, 5 mM DTT, and 1x cOmplete protease inhibitor cocktail tablet (Roche) per 40 ml fibrillization buffer. | ||||||||||||
グリッド | 材質: GOLD / メッシュ: 300 / 前処理 - タイプ: GLOW DISCHARGE / 前処理 - 時間: 60 sec. | ||||||||||||
凍結 | 凍結剤: ETHANE / チャンバー内湿度: 95 % / チャンバー内温度: 277 K / 装置: FEI VITROBOT MARK IV |
-電子顕微鏡法
顕微鏡 | TFS KRIOS |
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撮影 | フィルム・検出器のモデル: GATAN K3 BIOQUANTUM (6k x 4k) 平均電子線量: 48.7 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: SPOT SCAN / 撮影モード: BRIGHT FIELD / 最大 デフォーカス(公称値): 1.75 µm / 最小 デフォーカス(公称値): 0.0 µm |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |