+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 6tjx | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
タイトル | Cryo-EM structure of TypeII tau filaments extracted from the brains of individuals with Corticobasal degeneration | |||||||||
要素 | Microtubule-associated protein tau | |||||||||
キーワード | PROTEIN FIBRIL / tau protein / filament / cross-beta structure | |||||||||
機能・相同性 | 機能・相同性情報 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 / cellular response to reactive oxygen species / SH3 domain binding / microtubule cytoskeleton organization / activation of cysteine-type endopeptidase activity involved in apoptotic process / neuron projection development / microtubule cytoskeleton / 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 | 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 Å | |||||||||
データ登録者 | Zhang, W. / Murzin, A.G. / Falcon, B. / Shi, Y. / Goedert, M. / Scheres, S.H.W. | |||||||||
資金援助 | 英国, 2件
| |||||||||
引用 | ジャーナル: Nature / 年: 2020 タイトル: Novel tau filament fold in corticobasal degeneration. 著者: Wenjuan Zhang / Airi Tarutani / Kathy L Newell / Alexey G Murzin / Tomoyasu Matsubara / Benjamin Falcon / Ruben Vidal / Holly J Garringer / Yang Shi / Takeshi Ikeuchi / Shigeo Murayama / ...著者: Wenjuan Zhang / Airi Tarutani / Kathy L Newell / Alexey G Murzin / Tomoyasu Matsubara / Benjamin Falcon / Ruben Vidal / Holly J Garringer / Yang Shi / Takeshi Ikeuchi / Shigeo Murayama / Bernardino Ghetti / Masato Hasegawa / Michel Goedert / Sjors H W Scheres / 要旨: Corticobasal degeneration (CBD) is a neurodegenerative tauopathy-a class of disorders in which the tau protein forms insoluble inclusions in the brain-that is characterized by motor and cognitive ...Corticobasal degeneration (CBD) is a neurodegenerative tauopathy-a class of disorders in which the tau protein forms insoluble inclusions in the brain-that is characterized by motor and cognitive disturbances. The H1 haplotype of MAPT (the tau gene) is present in cases of CBD at a higher frequency than in controls, and genome-wide association studies have identified additional risk factors. By histology, astrocytic plaques are diagnostic of CBD; by SDS-PAGE, so too are detergent-insoluble, 37 kDa fragments of tau. Like progressive supranuclear palsy, globular glial tauopathy and argyrophilic grain disease, CBD is characterized by abundant filamentous tau inclusions that are made of isoforms with four microtubule-binding repeats. This distinguishes such '4R' tauopathies from Pick's disease (the filaments of which are made of three-repeat (3R) tau isoforms) and from Alzheimer's disease and chronic traumatic encephalopathy (CTE) (in which both 3R and 4R isoforms are found in the filaments). Here we use cryo-electron microscopy to analyse the structures of tau filaments extracted from the brains of three individuals with CBD. These filaments were identical between cases, but distinct from those seen in Alzheimer's disease, Pick's disease and CTE. The core of a CBD filament comprises residues lysine 274 to glutamate 380 of tau, spanning the last residue of the R1 repeat, the whole of the R2, R3 and R4 repeats, and 12 amino acids after R4. The core adopts a previously unseen four-layered fold, which encloses a large nonproteinaceous density. This density is surrounded by the side chains of lysine residues 290 and 294 from R2 and lysine 370 from the sequence after R4. | |||||||||
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 | 6tjx.cif.gz | 141.5 KB | 表示 | PDBx/mmCIF形式 |
---|---|---|---|---|
PDB形式 | pdb6tjx.ent.gz | 98.8 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 6tjx.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 | 6tjx_validation.pdf.gz | 1.1 MB | 表示 | wwPDB検証レポート |
---|---|---|---|---|
文書・詳細版 | 6tjx_full_validation.pdf.gz | 1.1 MB | 表示 | |
XML形式データ | 6tjx_validation.xml.gz | 33.1 KB | 表示 | |
CIF形式データ | 6tjx_validation.cif.gz | 48.3 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/tj/6tjx ftp://data.pdbj.org/pub/pdb/validation_reports/tj/6tjx | HTTPS FTP |
-関連構造データ
関連構造データ | 10514MC 6tjoC C: 同じ文献を引用 (文献) M: このデータのモデリングに利用したマップデータ |
---|---|
類似構造データ | |
電子顕微鏡画像生データ | EMPIAR-10340 (タイトル: Cryo-EM reconstruction of tau filaments extracted from the brains of three individuals with Corticobasal degeneration Data size: 2.8 TB Data #1: Unaligned movies for Case 1 [micrographs - multiframe] Data #2: Unaligned movies for Case 2 [micrographs - multiframe] Data #3: Unaligned movies for Case 3 [micrographs - multiframe]) |
-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) / 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: FILAMENT / 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 Frontal cortex of a patient with corticobasal degeneration. タイプ: COMPLEX 詳細: Corticobasal degeneration (CBD) is characterised by abundant filamentous tau inclusions that are made of isoforms with four microtubule-binding repeats (4R). Entity ID: all / 由来: NATURAL | |||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
分子量 | 値: 0.46 MDa / 実験値: NO | |||||||||||||||
由来(天然) | 生物種: Homo sapiens (ヒト) | |||||||||||||||
由来(組換発現) | 生物種: Escherichia coli (大腸菌) / 株: BL21(DE3) / プラスミド: pRK172 | |||||||||||||||
緩衝液 | pH: 7.4 / 詳細: 20 mM Tris, pH 7.4, 100mM NaCl | |||||||||||||||
緩衝液成分 |
| |||||||||||||||
試料 | 濃度: 2 mg/ml / 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES 詳細: The tau filaments were extracted from the Frontal cortex of a patient with corticobasal degeneration by using sarkosyl and ultracentrifuge. | |||||||||||||||
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 / 詳細: Blot force: -12 ; Blot time: 4s |
-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 / C2レンズ絞り径: 70 µm / アライメント法: ZEMLIN TABLEAU |
試料ホルダ | 凍結剤: NITROGEN 試料ホルダーモデル: FEI TITAN KRIOS AUTOGRID HOLDER |
撮影 | 平均露光時間: 10 sec. / 電子線照射量: 1.346 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) 撮影したグリッド数: 1 / 実像数: 2567 詳細: Images were collected in movie-mode at 40 frames every 10 seconds |
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: 20 eV |
画像スキャン | サンプリングサイズ: 5 µm / 横: 3838 / 縦: 3710 / 動画フレーム数/画像: 40 / 利用したフレーム数/画像: 1-40 |
-解析
EMソフトウェア |
| ||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
画像処理 | 詳細: Movie frames were gain-corrected, aligned, dose weighted and then summed into a single micrograph using MOTIONCOR2 (Zheng et al., 2017) | ||||||||||||||||||||||||||||||||||||||||||||
CTF補正 | 詳細: Aligned, non-dose-weighted micrographs were used to estimate the contrast transfer function (CTF) using CTFFIND4.1 タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||||||||||||||
らせん対称 | 回転角度/サブユニット: -0.61 ° / 軸方向距離/サブユニット: 4.786 Å / らせん対称軸の対称性: C2 | ||||||||||||||||||||||||||||||||||||||||||||
粒子像の選択 | 選択した粒子像数: 129812 / 詳細: Manually picked | ||||||||||||||||||||||||||||||||||||||||||||
3次元再構成 | 解像度: 3 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 20752 / クラス平均像の数: 1 / 対称性のタイプ: HELICAL | ||||||||||||||||||||||||||||||||||||||||||||
原子モデル構築 | B value: 25.75 / プロトコル: AB INITIO MODEL / 空間: RECIPROCAL / Target criteria: Fourier shell correlation 詳細: A stack of three consecutive monomers was refined to preserve nearest-neighbour interactions for the middle chain. Because most residues adopted cross strand conformation, hydrogen-bond ...詳細: A stack of three consecutive monomers was refined to preserve nearest-neighbour interactions for the middle chain. Because most residues adopted cross strand conformation, hydrogen-bond restraints were imposed to preserve a parallel, in-register hydrogen bonding pattern in earlier stages of Fourier-space refinements. Local symmetry restraints were imposed to keep all beta strand rungs identical. Side-chain clashes were detected using MOLPROBITY, and corrected by iterative cycles of real-space refinement in COOT and Fourier-space refinement in REFMAC and PHENIX. For each refined structure, separate model refinements were performed against a single half-map, and the resulting model was compared to the other half-map to confirm the absence of overfitting. |