8Y2Q

The cryo-EM structure of spermine induced a-synuclein fibril in Tris buffer.

8Y2Q の概要

• エントリーDOI: 10.2210/pdb8y2q/pdb
• EMDBエントリー: 38863
• 分子名称: Alpha-synuclein (1 entity in total)
• 機能のキーワード: amyloid, 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

Yao, Y.X.,Zhao, Q.Y.,Liu, C.,Li, D. (登録日: 2024-01-27, 公開日: 2025-01-29, 最終更新日: 2026-02-18)

主引用文献

Yao, Y.,Zhao, Q.,Tao, Y.,Liu, K.,Cao, T.,Chen, Z.,Liu, C.,Le, W.,Zhao, J.,Li, D.,Kang, W.
Different charged biopolymers induce alpha-synuclein to form fibrils with distinct structures.
J.Biol.Chem., 300:107862-107862, 2024

PubMed Abstract: The aggregation of α-synuclein (α-syn) into amyloid fibrils, a key process in the development of Parkinson's disease (PD) and other synucleinopathies, is influenced by a range of factors such as charged biopolymers, chaperones, and metabolites. However, the specific impacts of different biopolymers on α-syn fibril structure are not well understood. In our work, we found that different polyanions and polycations, such as polyphosphate (polyP), polyuridine (polyU), and polyamines (including putrescine, spermidine, and spermine), markedly altered the fibrillation kinetics of α-syn in vitro. Furthermore, the seeding assay revealed distinct cross-seeding capacities across different biopolymer-induced α-syn fibrils, suggesting the formation of structurally distinct strains under different conditions. Utilizing cryo-electron microscopy (cryo-EM), we further examined the detailed structural configuration of α-syn fibrils formed in the presence of these biopolymers. Notably, we found that while polyamines do not change the atomic structure of α-syn fibrils, polyU and polyP induce the formation of distinct amyloid fibrils, exhibiting a range of structural polymorphs. Our work offers valuable insights into how various charged biopolymers affect the aggregation process and the resultant structures of α-syn fibrils, thereby enhancing our understanding of the structural variations in α-syn fibrils across different pathological conditions.

PubMed: 39374778
DOI: 10.1016/j.jbc.2024.107862

実験手法

ELECTRON MICROSCOPY (2.8 Å)