EMDB/PDB/SASBDBから引用されている文献のデータベース

キーワード
構造解析手法	All X線回折 NMR 電子顕微鏡小角散乱中性子線回折線維回折粉末回折赤外分光 EPR FRET 理論モデルハイブリッド
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

タイトル	TDP-43 forms amyloid filaments with a distinct fold in type A FTLD-TDP.
ジャーナル・号・ページ	Nature, Vol. 620, Issue 7975, Page 898-903, Year 2023
掲載日	2023年8月2日
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 /
PubMed 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.
リンク	Nature / PubMed:37532939 / PubMed Central
手法	EM (らせん対称)
解像度	2.39 - 2.93 Å
構造データ	16628 8cg3 EMDB-16628, PDB-8cg3: Structure of TDP-43 amyloid filament from type A FTLD-TDP (variant 1) 手法: EM (らせん対称) / 解像度: 2.39 Å 16642 8cgg EMDB-16642, PDB-8cgg: Structure of TDP-43 amyloid filament from type A FTLD-TDP (variant 2) 手法: EM (らせん対称) / 解像度: 2.5 Å 16643 8cgh EMDB-16643, PDB-8cgh: Structure of TDP-43 amyloid filament from type A FTLD-TDP (variant 3) 手法: EM (らせん対称) / 解像度: 2.68 Å EMDB-16677: Structure of TDP-43 amyloid filament from type A FTLD-TDP (variant 1) 手法: EM (らせん対称) / 解像度: 2.65 Å EMDB-16681: Structure of TDP-43 amyloid filaments from type A FTLD-TDP (individual 2, variant 2) 手法: EM (らせん対称) / 解像度: 2.85 Å EMDB-16682: Structure of TDP-43 amyloid filaments from type A FTLD-TDP (individual 3, variant 1) 手法: EM (らせん対称) / 解像度: 2.93 Å
由来	homo sapiens (ヒト)
キーワード	PROTEIN FIBRIL / TDP-43 (TAR DNA結合タンパク質43) / FTD / FTLD / amyloid (アミロイド) / filaments / fibril (フィブリル) / neurodegeneration (神経変性疾患) / neurodegenerative disease (神経変性疾患) / RBP / RNA-binding protein (RNA結合タンパク質) / LCD / low-complexity domain / frontotemporal dementia (前頭側頭型認知症) / frontotemporal lobar degeneration / pathological / RNA BINDING PROTEIN (RNA結合タンパク質)