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基本情報
登録情報 | データベース: EMDB / ID: EMD-13710 | |||||||||
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タイトル | Structure of pathological TDP-43 filaments from ALS with FTLD (Individual 1, motor cortex) | |||||||||
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機能・相同性 | ![]() nuclear inner membrane organization / interchromatin granule / perichromatin fibrils / negative regulation by host of viral transcription / 3'-UTR-mediated mRNA destabilization / 3'-UTR-mediated mRNA stabilization / intracellular non-membrane-bounded organelle / pre-mRNA intronic binding / response to endoplasmic reticulum stress / RNA splicing ...nuclear inner membrane organization / interchromatin granule / perichromatin fibrils / negative regulation by host of viral transcription / 3'-UTR-mediated mRNA destabilization / 3'-UTR-mediated mRNA stabilization / intracellular non-membrane-bounded organelle / pre-mRNA intronic binding / response to endoplasmic reticulum stress / RNA splicing / molecular condensate scaffold activity / negative regulation of protein phosphorylation / mRNA 3'-UTR binding / regulation of circadian rhythm / regulation of protein stability / positive regulation of insulin secretion / positive regulation of protein import into nucleus / cytoplasmic stress granule / mRNA processing / rhythmic process / double-stranded DNA binding / regulation of gene expression / regulation of apoptotic process / amyloid fibril formation / regulation of cell cycle / nuclear speck / RNA polymerase II cis-regulatory region sequence-specific DNA binding / negative regulation of gene expression / lipid binding / chromatin / mitochondrion / DNA binding / RNA binding / nucleoplasm / identical protein binding / nucleus 類似検索 - 分子機能 | |||||||||
生物種 | ![]() | |||||||||
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: 2.94 Å | |||||||||
![]() | Arseni D / Hasegawa H | |||||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Structure of pathological TDP-43 filaments from ALS with FTLD. 著者: Diana Arseni / Masato Hasegawa / Alexey G Murzin / Fuyuki Kametani / Makoto Arai / Mari Yoshida / Benjamin Ryskeldi-Falcon / ![]() ![]() 要旨: The abnormal aggregation of TAR DNA-binding protein 43 kDa (TDP-43) in neurons and glia is the defining pathological hallmark of the neurodegenerative disease amyotrophic lateral sclerosis (ALS) ...The abnormal aggregation of TAR DNA-binding protein 43 kDa (TDP-43) in neurons and glia is the defining pathological hallmark of the neurodegenerative disease amyotrophic lateral sclerosis (ALS) and multiple forms of frontotemporal lobar degeneration (FTLD). It is also common in other diseases, including Alzheimer's and Parkinson's. No disease-modifying therapies exist for these conditions and early diagnosis is not possible. The structures of pathological TDP-43 aggregates are unknown. Here we used cryo-electron microscopy to determine the structures of aggregated TDP-43 in the frontal and motor cortices of an individual who had ALS with FTLD and from the frontal cortex of a second individual with the same diagnosis. An identical amyloid-like filament structure comprising a single protofilament was found in both brain regions and individuals. The ordered filament core spans residues 282-360 in the TDP-43 low-complexity domain and adopts a previously undescribed double-spiral-shaped fold, which shows no similarity to those of TDP-43 filaments formed in vitro. An abundance of glycine and neutral polar residues facilitates numerous turns and restricts β-strand length, which results in an absence of β-sheet stacking that is associated with cross-β amyloid structure. An uneven distribution of residues gives rise to structurally and chemically distinct surfaces that face external densities and suggest possible ligand-binding sites. This work enhances our understanding of the molecular pathogenesis of ALS and FTLD and informs the development of diagnostic and therapeutic agents that target aggregated TDP-43. | |||||||||
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構造の表示
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構造ビューア | EMマップ: ![]() ![]() ![]() |
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マップデータ | ![]() | 17.3 MB | ![]() | |
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ヘッダ (付随情報) | ![]() ![]() | 12.4 KB 12.4 KB | 表示 表示 | ![]() |
FSC (解像度算出) | ![]() | 9.1 KB | 表示 | ![]() |
画像 | ![]() | 100 KB | ||
マスクデータ | ![]() | 64 MB | ![]() | |
その他 | ![]() ![]() | 49.6 MB 49.5 MB | ||
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
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関連構造データ | ![]() 7py2C C: 同じ文献を引用 ( |
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電子顕微鏡画像生データ | ![]() Data size: 2.0 TB Data #1: Unaligned multiframe movies [micrographs - multiframe]) ![]() Data size: 2.9 TB Data #1: Unaligned multiframe movies [micrographs - multiframe]) |
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EMDBのページ | ![]() ![]() |
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「今月の分子」の関連する項目 |
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マップ
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投影像・断面図 | 画像のコントロール
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ボクセルのサイズ | X=Y=Z: 0.93 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
CCP4マップ ヘッダ情報:
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-添付データ
-マスク #1
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密度ヒストグラム |
-ハーフマップ: #1
ファイル | emd_13710_half_map_1.map | ||||||||||||
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密度ヒストグラム |
-ハーフマップ: #2
ファイル | emd_13710_half_map_2.map | ||||||||||||
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試料の構成要素
-全体 : Pathological TDP-43 filaments extracted from the motor cortex of ...
全体 | 名称: Pathological TDP-43 filaments extracted from the motor cortex of an individual that succumbed to ALS with FTLD. |
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要素 |
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-超分子 #1: Pathological TDP-43 filaments extracted from the motor cortex of ...
超分子 | 名称: Pathological TDP-43 filaments extracted from the motor cortex of an individual that succumbed to ALS with FTLD. タイプ: tissue / ID: 1 / 親要素: 0 / 含まれる分子: #1 |
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由来(天然) | 生物種: ![]() |
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
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![]() | らせん対称体再構成法 |
試料の集合状態 | filament |
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試料調製
緩衝液 | pH: 7.4 |
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凍結 | 凍結剤: ETHANE |
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電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
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撮影 | フィルム・検出器のモデル: GATAN K3 (6k x 4k) / 平均電子線量: 39.7 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: ![]() |
電子光学系 | 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELD |
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |