+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 6vi3 | |||||||||
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タイトル | Straight Filament from Alzheimer's Disease Human Brain Tissue | |||||||||
要素 | Microtubule-associated protein tau | |||||||||
キーワード | PROTEIN FIBRIL / Pathological amyloid fibril cross-beta fold parallel beta-sheets | |||||||||
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 / negative regulation of mitochondrial fission ...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 / negative regulation of mitochondrial fission / 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 / positive regulation of protein localization / 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 / microtubule polymerization / minor groove of adenine-thymine-rich DNA binding / lipoprotein particle binding / dynactin binding / glial cell projection / apolipoprotein binding / negative regulation of mitochondrial membrane potential / protein polymerization / 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 / cytoplasmic microtubule organization / supramolecular fiber organization / regulation of cellular response to heat / stress granule assembly / positive regulation of superoxide anion generation / regulation of calcium-mediated signaling / axon cytoplasm / positive regulation of microtubule polymerization / somatodendritic compartment / synapse assembly / cellular response to brain-derived neurotrophic factor stimulus / astrocyte activation / phosphatidylinositol binding / nuclear periphery / cellular response to nerve growth factor stimulus / protein phosphatase 2A binding / regulation of autophagy / response to lead ion / synapse organization / microglial cell activation / cellular response to reactive oxygen species / Hsp90 protein binding / PKR-mediated signaling / protein homooligomerization / regulation of synaptic plasticity / memory / activation of cysteine-type endopeptidase activity involved in apoptotic process / microtubule cytoskeleton organization / SH3 domain binding / cytoplasmic ribonucleoprotein granule / microtubule cytoskeleton / neuron projection development / cell-cell signaling / double-stranded DNA binding / protein-macromolecule adaptor activity / single-stranded DNA binding / actin binding / protein-folding chaperone binding / cellular response to heat / cell body / growth cone / microtubule binding / sequence-specific DNA binding / amyloid fibril formation / microtubule / learning or memory / dendritic spine / 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: 3.3 Å | |||||||||
データ登録者 | Arakhamia, T. / Lee, C.E. / Carlomagno, Y. / Duong, D.M. / Kundinger, S.R. / Wang, K. / Williams, D. / DeTure, M. / Dickson, D.W. / Cook, C.N. ...Arakhamia, T. / Lee, C.E. / Carlomagno, Y. / Duong, D.M. / Kundinger, S.R. / Wang, K. / Williams, D. / DeTure, M. / Dickson, D.W. / Cook, C.N. / Seyfried, N.T. / Petrucelli, L. / Fitzpatrick, A.W.P. | |||||||||
資金援助 | 米国, 2件
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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 |
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Remark 0 | THIS ENTRY 6VI3 REFLECTS AN ALTERNATIVE MODELING OF THE ORIGINAL DATA IN EMD-0260, DETERMINED BY ...THIS ENTRY 6VI3 REFLECTS AN ALTERNATIVE MODELING OF THE ORIGINAL DATA IN EMD-0260, DETERMINED BY Falcon, B. et al. |
-構造の表示
ムービー |
ムービービューア |
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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 | 6vi3.cif.gz | 36.5 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb6vi3.ent.gz | 24.9 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 6vi3.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 | 6vi3_validation.pdf.gz | 1.3 MB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 6vi3_full_validation.pdf.gz | 1.3 MB | 表示 | |
XML形式データ | 6vi3_validation.xml.gz | 23.1 KB | 表示 | |
CIF形式データ | 6vi3_validation.cif.gz | 31.1 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/vi/6vi3 ftp://data.pdbj.org/pub/pdb/validation_reports/vi/6vi3 | HTTPS FTP |
-関連構造データ
-リンク
-集合体
登録構造単位 |
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1 |
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-要素
#1: タンパク質 | 分子量: 8370.578 Da / 分子数: 2 / 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 / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: P10636 #2: 化合物 | 研究の焦点であるリガンドがあるか | Y | |
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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: 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: Straight Filament from Alzheimer's Disease Human Brain Tissue タイプ: TISSUE / Entity ID: #1 / 由来: NATURAL |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
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 |
試料支持 | 詳細: unspecified |
急速凍結 | 凍結剤: ETHANE |
-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: 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 |
撮影 | 電子線照射量: 60 e/Å2 フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) |
-解析
CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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らせん対称 | 回転角度/サブユニット: -1.04 ° / 軸方向距離/サブユニット: 4.76 Å / らせん対称軸の対称性: C1 |
3次元再構成 | 解像度: 3.3 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 62782 / 対称性のタイプ: HELICAL |