6L4S

cryo-em structure of alpha-synuclein fiber mutation type E46K

6L4S の概要

• エントリーDOI: 10.2210/pdb6l4s/pdb
• EMDBエントリー: 0833
• 分子名称: Alpha-synuclein (1 entity in total)
• 機能のキーワード: alpha-syn fiber, parkinson disease, 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: 32412.94

構造登録者

Li, Y.W.,Zhao, K.,Liu, C.,Li, X. (登録日: 2019-10-21, 公開日: 2020-04-29, 最終更新日: 2024-05-29)

主引用文献

Zhao, K.,Li, Y.,Liu, Z.,Long, H.,Zhao, C.,Luo, F.,Sun, Y.,Tao, Y.,Su, X.D.,Li, D.,Li, X.,Liu, C.
Parkinson's disease associated mutation E46K of alpha-synuclein triggers the formation of a distinct fibril structure.
Nat Commun, 11:2643-2643, 2020

PubMed Abstract: Amyloid aggregation of α-synuclein (α-syn) is closely associated with Parkinson's disease (PD) and other synucleinopathies. Several single amino-acid mutations (e.g. E46K) of α-syn have been identified causative to the early onset of familial PD. Here, we report the cryo-EM structure of an α-syn fibril formed by N-terminally acetylated E46K mutant α-syn (Ac-E46K). The fibril structure represents a distinct fold of α-syn, which demonstrates that the E46K mutation breaks the electrostatic interactions in the wild type (WT) α-syn fibril and thus triggers the rearrangement of the overall structure. Furthermore, we show that the Ac-E46K fibril is less resistant to harsh conditions and protease cleavage, and more prone to be fragmented with an enhanced seeding capability than that of the WT fibril. Our work provides a structural view to the severe pathology of the PD familial mutation E46K of α-syn and highlights the importance of electrostatic interactions in defining the fibril polymorphs.

PubMed: 32457390
DOI: 10.1038/s41467-020-16386-3

実験手法

ELECTRON MICROSCOPY (3.37 Å)