9EWV

mouse alpha-synuclein

9EWV の概要

• エントリーDOI: 10.2210/pdb9ewv/pdb
• EMDBエントリー: 50023
• 分子名称: Alpha-synuclein (1 entity in total)
• 機能のキーワード: alpha-synuclein, recombinant, fibril, protein fibril
• 由来する生物種: Mus musculus (house mouse)
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 174014.22

構造登録者

Tatli, M.,Stahlberg, H. (登録日: 2024-04-04, 公開日: 2024-11-13)

主引用文献

Sokratian, A.,Zhou, Y.,Tatli, M.,Burbidge, K.J.,Xu, E.,Viverette, E.,Donzelli, S.,Duda, A.M.,Yuan, Y.,Li, H.,Strader, S.,Patel, N.,Shiell, L.,Malankhanova, T.,Chen, O.,Mazzulli, J.R.,Perera, L.,Stahlberg, H.,Borgnia, M.,Bartesaghi, A.,Lashuel, H.A.,West, A.B.
Mouse alpha-synuclein fibrils are structurally and functionally distinct from human fibrils associated with Lewy body diseases.
Sci Adv, 10:eadq3539-eadq3539, 2024

PubMed Abstract: The intricate process of α-synuclein aggregation and fibrillization holds pivotal roles in Parkinson's disease (PD) and multiple system atrophy (MSA). While mouse α-synuclein can fibrillize in vitro, whether these fibrils commonly used in research to induce this process or form can reproduce structures in the human brain remains unknown. Here, we report the first atomic structure of mouse α-synuclein fibrils, which was solved in parallel by two independent teams. The structure shows striking similarity to MSA-amplified and PD-associated E46K fibrils. However, mouse α-synuclein fibrils display altered packing arrangements, reduced hydrophobicity, and heightened fragmentation sensitivity and evoke only weak immunological responses. Furthermore, mouse α-synuclein fibrils exhibit exacerbated pathological spread in neurons and humanized α-synuclein mice. These findings provide critical insights into the structural underpinnings of α-synuclein pathogenicity and emphasize a need to reassess the role of mouse α-synuclein fibrils in the development of related diagnostic probes and therapeutic interventions.

PubMed: 39485845
DOI: 10.1126/sciadv.adq3539

実験手法

ELECTRON MICROSCOPY (2.9 Å)