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- EMDB-16628: Structure of TDP-43 amyloid filament from type A FTLD-TDP (variant 1) -
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データを開く
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基本情報
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タイトル | Structure of TDP-43 amyloid filament from type A FTLD-TDP (variant 1) | |||||||||
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![]() | TDP-43 / FTD / FTLD / amyloid / filaments / fibril / neurodegeneration / neurodegenerative disease / RBP / RNA-binding protein / LCD / low-complexity domain / frontotemporal dementia / frontotemporal lobar degeneration / pathological / RNA BINDING PROTEIN / PROTEIN FIBRIL | |||||||||
機能・相同性 | ![]() nuclear inner membrane organization / interchromatin granule / perichromatin fibrils / 3'-UTR-mediated mRNA destabilization / 3'-UTR-mediated mRNA stabilization / intracellular non-membrane-bounded organelle / negative regulation by host of viral transcription / pre-mRNA intronic binding / response to endoplasmic reticulum stress / RNA splicing ...nuclear inner membrane organization / interchromatin granule / perichromatin fibrils / 3'-UTR-mediated mRNA destabilization / 3'-UTR-mediated mRNA stabilization / intracellular non-membrane-bounded organelle / negative regulation by host of viral transcription / 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 protein stability / positive regulation of insulin secretion / regulation of circadian rhythm / cytoplasmic stress granule / positive regulation of protein import into nucleus / mRNA processing / rhythmic process / regulation of gene expression / double-stranded DNA binding / 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: 2.39 Å | |||||||||
![]() | Arseni D / Ryskeldi-Falcon B | |||||||||
資金援助 | ![]()
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![]() | ![]() タイトル: TDP-43 forms amyloid filaments with a distinct fold in type A FTLD-TDP. 著者: Diana Arseni / Renren Chen / Alexey G Murzin / Sew Y Peak-Chew / Holly J Garringer / Kathy L Newell / Fuyuki Kametani / Andrew C Robinson / Ruben Vidal / Bernardino Ghetti / Masato Hasegawa / ...著者: Diana Arseni / Renren Chen / Alexey G Murzin / Sew Y Peak-Chew / Holly J Garringer / Kathy L Newell / Fuyuki Kametani / Andrew C Robinson / Ruben Vidal / Bernardino Ghetti / Masato Hasegawa / Benjamin Ryskeldi-Falcon / ![]() ![]() ![]() 要旨: The abnormal assembly of TAR DNA-binding protein 43 (TDP-43) in neuronal and glial cells characterizes nearly all cases of amyotrophic lateral sclerosis (ALS) and around half of cases of ...The abnormal assembly of TAR DNA-binding protein 43 (TDP-43) in neuronal and glial cells characterizes nearly all cases of amyotrophic lateral sclerosis (ALS) and around half of cases of frontotemporal lobar degeneration (FTLD). A causal role for TDP-43 assembly in neurodegeneration is evidenced by dominantly inherited missense mutations in TARDBP, the gene encoding TDP-43, that promote assembly and give rise to ALS and FTLD. At least four types (A-D) of FTLD with TDP-43 pathology (FTLD-TDP) are defined by distinct brain distributions of assembled TDP-43 and are associated with different clinical presentations of frontotemporal dementia. We previously showed, using cryo-electron microscopy, that TDP-43 assembles into amyloid filaments in ALS and type B FTLD-TDP. However, the structures of assembled TDP-43 in FTLD without ALS remained unknown. Here we report the cryo-electron microscopy structures of assembled TDP-43 from the brains of three individuals with the most common type of FTLD-TDP, type A. TDP-43 formed amyloid filaments with a new fold that was the same across individuals, indicating that this fold may characterize type A FTLD-TDP. The fold resembles a chevron badge and is unlike the double-spiral-shaped fold of ALS and type B FTLD-TDP, establishing that distinct filament folds of TDP-43 characterize different neurodegenerative conditions. The structures, in combination with mass spectrometry, led to the identification of two new post-translational modifications of assembled TDP-43, citrullination and monomethylation of R293, and indicate that they may facilitate filament formation and observed structural variation in individual filaments. The structures of TDP-43 filaments from type A FTLD-TDP will guide mechanistic studies of TDP-43 assembly, as well as the development of diagnostic and therapeutic compounds for TDP-43 proteinopathies. | |||||||||
履歴 |
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構造の表示
添付画像 |
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ダウンロードとリンク
-EMDBアーカイブ
マップデータ | ![]() | 19.4 MB | ![]() | |
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ヘッダ (付随情報) | ![]() ![]() | 14.7 KB 14.7 KB | 表示 表示 | ![]() |
FSC (解像度算出) | ![]() | 9.1 KB | 表示 | ![]() |
画像 | ![]() | 36.3 KB | ||
マスクデータ | ![]() | 64 MB | ![]() | |
その他 | ![]() ![]() | 49.6 MB 49.6 MB | ||
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-関連構造データ
関連構造データ | ![]() 8cg3MC ![]() 8cggC ![]() 8cghC M: このマップから作成された原子モデル 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 ![]() |
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リンク
EMDBのページ | ![]() ![]() |
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マップ
ファイル | ![]() | ||||||||||||||||||||
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ボクセルのサイズ | X=Y=Z: 0.86 Å | ||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||
詳細 | EMDB XML:
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-添付データ
-マスク #1
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投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: #2
ファイル | emd_16628_half_map_1.map | ||||||||||||
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投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: #1
ファイル | emd_16628_half_map_2.map | ||||||||||||
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投影像・断面図 |
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密度ヒストグラム |
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試料の構成要素
-全体 : TDP-43 amyloid filaments extracted from the frontal cortex of an ...
全体 | 名称: TDP-43 amyloid filaments extracted from the frontal cortex of an individual with type A FTLD-TDP |
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要素 |
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-超分子 #1: TDP-43 amyloid filaments extracted from the frontal cortex of an ...
超分子 | 名称: TDP-43 amyloid filaments extracted from the frontal cortex of an individual with type A FTLD-TDP タイプ: tissue / ID: 1 / 親要素: 0 / 含まれる分子: all |
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由来(天然) | 生物種: ![]() |
-分子 #1: TAR DNA-binding protein 43
分子 | 名称: TAR DNA-binding protein 43 / タイプ: protein_or_peptide / ID: 1 / コピー数: 5 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 44.784742 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: MSEYIRVTED ENDEPIEIPS EDDGTVLLST VTAQFPGACG LRYRNPVSQC MRGVRLVEGI LHAPDAGWGN LVYVVNYPKD NKRKMDETD ASSAVKVKRA VQKTSDLIVL GLPWKTTEQD LKEYFSTFGE VLMVQVKKDL KTGHSKGFGF VRFTEYETQV K VMSQRHMI ...文字列: MSEYIRVTED ENDEPIEIPS EDDGTVLLST VTAQFPGACG LRYRNPVSQC MRGVRLVEGI LHAPDAGWGN LVYVVNYPKD NKRKMDETD ASSAVKVKRA VQKTSDLIVL GLPWKTTEQD LKEYFSTFGE VLMVQVKKDL KTGHSKGFGF VRFTEYETQV K VMSQRHMI DGRWCDCKLP NSKQSQDEPL RSRKVFVGRC TEDMTEDELR EFFSQYGDVM DVFIPKPFRA FAFVTFADDQ IA QSLCGED LIIKGISVHI SNAEPKHNSN RQLERSGRFG GNPGGFGNQG GFGNSRGGGA GLGNNQGSNM GGGMNFGAFS INP AMMAAA QAALQSSWGM MGMLASQQNQ SGPSGNNQNQ GNMQREPNQA FGSGNNSYSG SNSGAAIGWG SASNAGSGSG FNGG FGSSM DSKSSGWGM UniProtKB: TAR DNA-binding protein 43 |
-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: 35.896 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 / 最大 デフォーカス(公称値): 2.2 µm / 最小 デフォーカス(公称値): 1.0 µm |
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |