+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 6hre | ||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
タイトル | Paired helical filament from sporadic Alzheimer's disease brain | ||||||||||||||||||
要素 | Microtubule-associated protein tau | ||||||||||||||||||
キーワード | PROTEIN FIBRIL / Tau / helical / filament / fibril / amyloid / Alzheimer's disease / PHF / paired helical filament / NFT / neurofibrillary tangly | ||||||||||||||||||
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 | 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: 3.2 Å | ||||||||||||||||||
データ登録者 | Falcon, B. / Zhang, W. / Schweighauser, M. / Murzin, A.G. / Vidal, R. / Garringer, H.J. / Ghetti, B. / Scheres, S.H.W. / Goedert, M. | ||||||||||||||||||
資金援助 | 英国, 米国, 5件
| ||||||||||||||||||
引用 | ジャーナル: Acta Neuropathol / 年: 2018 タイトル: Tau filaments from multiple cases of sporadic and inherited Alzheimer's disease adopt a common fold. 著者: Benjamin Falcon / Wenjuan Zhang / Manuel Schweighauser / Alexey G Murzin / Ruben Vidal / Holly J Garringer / Bernardino Ghetti / Sjors H W Scheres / Michel Goedert / 要旨: The ordered assembly of tau protein into abnormal filaments is a defining characteristic of Alzheimer's disease (AD) and other neurodegenerative disorders. It is not known if the structures of tau ...The ordered assembly of tau protein into abnormal filaments is a defining characteristic of Alzheimer's disease (AD) and other neurodegenerative disorders. It is not known if the structures of tau filaments vary within, or between, the brains of individuals with AD. We used a combination of electron cryo-microscopy (cryo-EM) and immuno-gold negative-stain electron microscopy (immuno-EM) to determine the structures of paired helical filaments (PHFs) and straight filaments (SFs) from the frontal cortex of 17 cases of AD (15 sporadic and 2 inherited) and 2 cases of atypical AD (posterior cortical atrophy). The high-resolution structures of PHFs and SFs from the frontal cortex of 3 cases of AD, 2 sporadic and 1 inherited, were determined by cryo-EM. We also used immuno-EM to study the PHFs and SFs from a number of cortical and subcortical brain regions. PHFs outnumbered SFs in all AD cases. By cryo-EM, PHFs and SFs were made of two C-shaped protofilaments with a combined cross-β/β-helix structure, as described previously for one case of AD. The higher resolution structures obtained here showed two additional amino acids at each end of the protofilament. The immuno-EM findings, which indicated the presence of repeats 3 and 4, but not of the N-terminal regions of repeats 1 and 2, of tau in the filament cores of all AD cases, were consistent with the cryo-EM results. These findings show that there is no significant variation in tau filament structures between individuals with AD. This knowledge will be crucial for understanding the mechanisms that underlie tau filament formation and for developing novel diagnostics and therapies. | ||||||||||||||||||
履歴 |
|
-構造の表示
ムービー |
ムービービューア |
---|---|
構造ビューア | 分子: MolmilJmol/JSmol |
-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 6hre.cif.gz | 125 KB | 表示 | PDBx/mmCIF形式 |
---|---|---|---|---|
PDB形式 | pdb6hre.ent.gz | 83.2 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 6hre.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
文書・要旨 | 6hre_validation.pdf.gz | 1.2 MB | 表示 | wwPDB検証レポート |
---|---|---|---|---|
文書・詳細版 | 6hre_full_validation.pdf.gz | 1.2 MB | 表示 | |
XML形式データ | 6hre_validation.xml.gz | 28.2 KB | 表示 | |
CIF形式データ | 6hre_validation.cif.gz | 39.8 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/hr/6hre ftp://data.pdbj.org/pub/pdb/validation_reports/hr/6hre | HTTPS FTP |
-関連構造データ
関連構造データ | 0259MC 0260C 6hrfC 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 (文献) |
---|---|
類似構造データ | |
電子顕微鏡画像生データ | EMPIAR-10230 (タイトル: Cryo electron microscopy of tau filaments from sporadic Alzheimer's disease brain Data size: 27.0 Data #1: Dose-weighted micrographs of tau filaments from sporadic Alzheimer's disease brain (case 2) [micrographs - single frame]) |
-リンク
-集合体
登録構造単位 |
|
---|---|
1 |
|
-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) Homo sapiens (ヒト) / Plasmid details: Post-mortem / 組織: Brain / 参照: UniProt: P10636 |
---|
-実験情報
-実験
実験 | 手法: 電子顕微鏡法 |
---|---|
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 |
-試料調製
構成要素 | 名称: Tau filaments extracted from the frontotemporal cortex of a patient with sporadic Alzheimer's disease タイプ: TISSUE / Entity ID: all / 由来: NATURAL | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
由来(天然) | 生物種: Homo sapiens (ヒト) / 器官: Brain / 組織: Frontotemporal cortex | ||||||||||||
緩衝液 | pH: 7.4 | ||||||||||||
緩衝液成分 |
| ||||||||||||
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 / 詳細: Dispersed filaments | ||||||||||||
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 K |
-電子顕微鏡撮影
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
---|---|
顕微鏡 | モデル: FEI TITAN 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 / 検出モード: COUNTING フィルム・検出器のモデル: GATAN K2 QUANTUM (4k x 4k) |
電子光学装置 | エネルギーフィルター名称: GIF Quantum LS |
-解析
EMソフトウェア |
| ||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
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: 179.45 ° / 軸方向距離/サブユニット: 2.37 Å / らせん対称軸の対称性: C1 | ||||||||||||||||||||||||
3次元再構成 | 解像度: 3.2 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 95917 / 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. |