7C1D

Cryo-EM structure of the hE46K cross-seeded hWT alpha-synuclein fibril

7C1D の概要

• エントリーDOI: 10.2210/pdb7c1d/pdb
• EMDBエントリー: 30269
• 分子名称: Alpha-synuclein (1 entity in total)
• 機能のキーワード: amyloid fibril, protein fibril
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 86856.65

構造登録者

Sun, Y.P.,Zhao, K.,Liu, C. (登録日: 2020-05-03, 公開日: 2021-05-05, 最終更新日: 2024-05-29)

主引用文献

Long, H.,Zheng, W.,Liu, Y.,Sun, Y.,Zhao, K.,Liu, Z.,Xia, W.,Lv, S.,Liu, Z.,Li, D.,He, K.W.,Liu, C.
Wild-type alpha-synuclein inherits the structure and exacerbated neuropathology of E46K mutant fibril strain by cross-seeding.
Proc.Natl.Acad.Sci.USA, 118:-, 2021

PubMed Abstract: Heterozygous point mutations of α-synuclein (α-syn) have been linked to the early onset and rapid progression of familial Parkinson's diseases (fPD). However, the interplay between hereditary mutant and wild-type (WT) α-syn and its role in the exacerbated pathology of α-syn in fPD progression are poorly understood. Here, we find that WT mice inoculated with the human E46K mutant α-syn fibril (hE46K) strain develop early-onset motor deficit and morphologically different α-syn aggregation compared with those inoculated with the human WT fibril (hWT) strain. By using cryo-electron microscopy, we reveal at the near-atomic level that the hE46K strain induces both human and mouse WT α-syn monomers to form the fibril structure of the hE46K strain. Moreover, the induced hWT strain inherits most of the pathological traits of the hE46K strain as well. Our work suggests that the structural and pathological features of mutant strains could be propagated by the WT α-syn in such a way that the mutant pathology would be amplified in fPD.

PubMed: 33972418
DOI: 10.1073/pnas.2012435118

実験手法

ELECTRON MICROSCOPY (3.8 Å)