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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: 9shs | ||||||||||||||||||||||||
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| タイトル | Head to Head tau filament with the Alzheimer's fold | ||||||||||||||||||||||||
要素 | Isoform Tau-D of Microtubule-associated protein tau | ||||||||||||||||||||||||
キーワード | PROTEIN FIBRIL / TAU / HELICAL / FILAMENT / FIBRIL / AMYLOID / ALZHEIMER'S DISEASE / PAIRED HELICAL FILAMENT | ||||||||||||||||||||||||
| 機能・相同性 | 機能・相同性情報plus-end-directed organelle transport along microtubule / histone-dependent DNA binding / negative regulation of protein localization to mitochondrion / neurofibrillary tangle / microtubule lateral binding / axonal transport / tubulin complex / positive regulation of protein localization to synapse / phosphatidylinositol bisphosphate binding / generation of neurons ...plus-end-directed organelle transport along microtubule / histone-dependent DNA binding / negative regulation of protein localization to mitochondrion / neurofibrillary tangle / microtubule lateral binding / axonal transport / tubulin complex / positive regulation of protein localization to synapse / phosphatidylinositol bisphosphate binding / generation of neurons / rRNA metabolic process / axonal transport of mitochondrion / regulation of mitochondrial fission / axon development / regulation of microtubule-based movement / regulation of chromosome organization / intracellular distribution of mitochondria / central nervous system neuron development / minor groove of adenine-thymine-rich DNA binding / lipoprotein particle binding / microtubule polymerization / negative regulation of mitochondrial membrane potential / regulation of microtubule polymerization / dynactin binding / apolipoprotein binding / protein polymerization / main axon / axolemma / Caspase-mediated cleavage of cytoskeletal proteins / regulation of microtubule polymerization or depolymerization / negative regulation of mitochondrial fission / glial cell projection / neurofibrillary tangle assembly / positive regulation of axon extension / positive regulation of microtubule polymerization / regulation of cellular response to heat / Activation of AMPK downstream of NMDARs / positive regulation of protein localization / positive regulation of superoxide anion generation / cellular response to brain-derived neurotrophic factor stimulus / regulation of long-term synaptic depression / supramolecular fiber organization / cytoplasmic microtubule organization / regulation of calcium-mediated signaling / somatodendritic compartment / axon cytoplasm / synapse assembly / astrocyte activation / phosphatidylinositol binding / nuclear periphery / enzyme inhibitor activity / protein phosphatase 2A binding / stress granule assembly / regulation of microtubule cytoskeleton organization / regulation of autophagy / cellular response to reactive oxygen species / microglial cell activation / cellular response to nerve growth factor stimulus / Hsp90 protein binding / protein homooligomerization / SH3 domain binding / PKR-mediated signaling / regulation of synaptic plasticity / synapse organization / response to lead ion / microtubule cytoskeleton organization / memory / cytoplasmic ribonucleoprotein granule / neuron projection development / cell-cell signaling / single-stranded DNA binding / cellular response to heat / growth cone / protein-folding chaperone binding / microtubule cytoskeleton / actin binding / cell body / double-stranded DNA binding / microtubule binding / sequence-specific DNA binding / amyloid fibril formation / dendritic spine / microtubule / protein-macromolecule adaptor activity / learning or memory / neuron projection / membrane raft / negative regulation of gene expression / axon / neuronal cell body / DNA damage response / dendrite / protein kinase binding / enzyme binding / mitochondrion / DNA binding / RNA binding / extracellular region / identical protein binding / nucleus 類似検索 - 分子機能 | ||||||||||||||||||||||||
| 生物種 | Homo sapiens (ヒト) | ||||||||||||||||||||||||
| 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 | ||||||||||||||||||||||||
データ登録者 | Scheres, S.H.W. / Goedert, M. | ||||||||||||||||||||||||
| 資金援助 | 英国, 1件
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引用 | ジャーナル: J Biol Chem / 年: 2025タイトル: Seeding biosensor cell line that reproduces the Alzheimer tau fold. 著者: Taxiarchis Katsinelos / Sofia Lövestam / Chao Qi / Benjamin Ryskeldi-Falcon / Jennifer A Macdonald / Gabriel Stephenson / Bernardino Ghetti / Ann McKee / Sjors H W Scheres / Michel Goedert / ![]() 要旨: The assembly of tau protein into amyloid filaments through templated seeding is believed to underlie the propagation of pathology in neurodegenerative diseases, such as Alzheimer's disease (AD) and ...The assembly of tau protein into amyloid filaments through templated seeding is believed to underlie the propagation of pathology in neurodegenerative diseases, such as Alzheimer's disease (AD) and other tauopathies. A commonly used model system for studying this process is through the induction of tau filament formation in cultured cells following the addition of tau seeds isolated from the human brain. However, little is known about the structures of seeded filaments; some biosensor cell lines are unable to reproduce the tau filament structures from AD, because they overexpress tau fragments that do not cover the whole of the ordered filament core. Here, we describe a novel tau seeding biosensor model in human embryonic kidney 293T cells that overexpress residues K297-E391 of human 4R tau. The construct contains an N-terminal hemagglutinin tag, which allows the specific detection of the amplified template. The biosensor cells detected filaments seeded by material from sporadic three-repeat (3R) + four-repeat (4R) tauopathies, with little activity by seeds from 3R-only or 4R-only tauopathies. The sensitivity of seed detection from 3R + 4R tauopathies in our system was similar to or higher than for previously reported biosensors. We also structurally characterized the AD-seeded tau filaments by cryo-EM. Most of the cell-derived filaments consisted of two protofilaments with the Alzheimer's fold but with a "head-to-head" interprotofilament packing. Our results establish a sensitive biosensor cell line with specificity toward seeds from 3R + 4R tauopathies. | ||||||||||||||||||||||||
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構造の表示
| 構造ビューア | 分子: Molmil Jmol/JSmol |
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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 | 9shs.cif.gz | 165.6 KB | 表示 | PDBx/mmCIF形式 |
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| PDB形式 | pdb9shs.ent.gz | 137.5 KB | 表示 | PDB形式 |
| PDBx/mmJSON形式 | 9shs.json.gz | ツリー表示 | PDBx/mmJSON形式 | |
| その他 | その他のダウンロード |
-検証レポート
| アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/sh/9shs ftp://data.pdbj.org/pub/pdb/validation_reports/sh/9shs | HTTPS FTP |
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-関連構造データ
| 関連構造データ | ![]() 54909MC M: このデータのモデリングに利用したマップデータ 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 F&H 検索 |
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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: 8241.465 Da / 分子数: 6 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: MAPT, MAPTL, MTBT1, TAU / Cell (発現宿主): HEK293T / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: P10636Has protein modification | N | |
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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: HELICAL ARRAY / 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 filament / タイプ: COMPLEX / Entity ID: all / 由来: RECOMBINANT |
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| 由来(天然) | 生物種: Homo sapiens (ヒト) |
| 由来(組換発現) | 生物種: Homo sapiens (ヒト) / 細胞: HEK293T |
| 緩衝液 | pH: 7.4 |
| 試料 | 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES |
| 急速凍結 | 凍結剤: ETHANE |
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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: TFS KRIOS |
| 電子銃 | 電子線源: FIELD EMISSION GUN / 加速電圧: 300 kV / 照射モード: FLOOD BEAM |
| 電子レンズ | モード: BRIGHT FIELD / 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 | 電子線照射量: 1.2 e/Å2 フィルム・検出器のモデル: GATAN K3 BIOQUANTUM (6k x 4k) |
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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: -0.93 ° / 軸方向距離/サブユニット: 4.83 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: 22000 / 対称性のタイプ: HELICAL | ||||||||||||
| 原子モデル構築 | B value: 72.8 / プロトコル: AB INITIO MODEL / 空間: RECIPROCAL / Target criteria: FOURIER SHELL CORRELATION 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- ...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. | ||||||||||||
| 精密化 | 最高解像度: 3.4 Å |
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万見について




Homo sapiens (ヒト)
英国, 1件
引用

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FIELD EMISSION GUN