6CU8

Alpha Synuclein fibril formed by full length protein - Twister Polymorph

6CU8 の概要

• エントリーDOI: 10.2210/pdb6cu8/pdb
• 関連するPDBエントリー: 6CU7
• EMDBエントリー: 7619
• 分子名称: Alpha-synuclein (1 entity in total)
• 機能のキーワード: parkinson's disease, synucleinopathy, amyloid aggregation, fibril polymorphism, 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: 144761.08

構造登録者

Li, B.,Hatami, A.,Ge, P.,Murray, K.A.,Sheth, P.,Zhang, M.,Nair, G.,Sawaya, M.R.,Zhu, C.,Broad, M.,Shin, W.S.,Ye, S.,John, V.,Eisenberg, D.S.,Zhou, Z.H.,Jiang, L. (登録日: 2018-03-23, 公開日: 2018-09-12, 最終更新日: 2024-03-13)

主引用文献

Li, B.,Ge, P.,Murray, K.A.,Sheth, P.,Zhang, M.,Nair, G.,Sawaya, M.R.,Shin, W.S.,Boyer, D.R.,Ye, S.,Eisenberg, D.S.,Zhou, Z.H.,Jiang, L.
Cryo-EM of full-length alpha-synuclein reveals fibril polymorphs with a common structural kernel.
Nat Commun, 9:3609-3609, 2018

PubMed Abstract: α-Synuclein (aSyn) fibrillar polymorphs have distinct in vitro and in vivo seeding activities, contributing differently to synucleinopathies. Despite numerous prior attempts, how polymorphic aSyn fibrils differ in atomic structure remains elusive. Here, we present fibril polymorphs from the full-length recombinant human aSyn and their seeding capacity and cytotoxicity in vitro. By cryo-electron microscopy helical reconstruction, we determine the structures of the two predominant species, a rod and a twister, both at 3.7 Å resolution. Our atomic models reveal that both polymorphs share a kernel structure of a bent β-arch, but differ in their inter-protofilament interfaces. Thus, different packing of the same kernel structure gives rise to distinct fibril polymorphs. Analyses of disease-related familial mutations suggest their potential contribution to the pathogenesis of synucleinopathies by altering population distribution of the fibril polymorphs. Drug design targeting amyloid fibrils in neurodegenerative diseases should consider the formation and distribution of concurrent fibril polymorphs.

PubMed: 30190461
DOI: 10.1038/s41467-018-05971-2

実験手法

ELECTRON MICROSCOPY (3.6 Å)