7SAR

Cryo-EM structure of TMEM106B fibrils extracted from a FTLD-TDP patient, polymorph 2

7SAR の概要

• エントリーDOI: 10.2210/pdb7sar/pdb
• EMDBエントリー: 24954
• 分子名称: Transmembrane protein 106B, 2-acetamido-2-deoxy-beta-D-glucopyranose (2 entities in total)
• 機能のキーワード: tmem106b, ftld-tdp, amyloid, protein fibril
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 10
• 化学式量合計: 320411.50

構造登録者

Cao, Q.,Jiang, Y.,Sawaya, M.R.,Eisenberg, D.S. (登録日: 2021-09-23, 公開日: 2022-03-09, 最終更新日: 2024-10-23)

主引用文献

Jiang, Y.X.,Cao, Q.,Sawaya, M.R.,Abskharon, R.,Ge, P.,DeTure, M.,Dickson, D.W.,Fu, J.Y.,Ogorzalek Loo, R.R.,Loo, J.A.,Eisenberg, D.S.
Amyloid fibrils in FTLD-TDP are composed of TMEM106B and not TDP-43.
Nature, 605:304-309, 2022

PubMed Abstract: Frontotemporal lobar degeneration (FTLD) is the third most common neurodegenerative condition after Alzheimer's and Parkinson's diseases. FTLD typically presents in 45 to 64 year olds with behavioural changes or progressive decline of language skills. The subtype FTLD-TDP is characterized by certain clinical symptoms and pathological neuronal inclusions with TAR DNA-binding protein (TDP-43) immunoreactivity. Here we extracted amyloid fibrils from brains of four patients representing four of the five FTLD-TDP subclasses, and determined their structures by cryo-electron microscopy. Unexpectedly, all amyloid fibrils examined were composed of a 135-residue carboxy-terminal fragment of transmembrane protein 106B (TMEM106B), a lysosomal membrane protein previously implicated as a genetic risk factor for FTLD-TDP. In addition to TMEM106B fibrils, we detected abundant non-fibrillar aggregated TDP-43 by immunogold labelling. Our observations confirm that FTLD-TDP is associated with amyloid fibrils, and that the fibrils are formed by TMEM106B rather than TDP-43.

PubMed: 35344984
DOI: 10.1038/s41586-022-04670-9

実験手法

ELECTRON MICROSCOPY (3.2 Å)