8AZ3

IAPP S20G growth-phase fibril polymorph 4PF-CU

8AZ3 の概要

• エントリーDOI: 10.2210/pdb8az3/pdb
• 関連するPDBエントリー: 8AZ0 8AZ1 8AZ2
• EMDBエントリー: 15728 15729 15730 15731 15754
• 分子名称: Islet amyloid polypeptide (1 entity in total)
• 機能のキーワード: amyloid, fibril, helical, cross-beta, amylin, polymorph, islet, protein fibril, diabetes
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 20
• 化学式量合計: 77545.72

構造登録者

Wilkinson, M.,Xu, Y.,Gallardo, R.,Radford, S.E.,Ranson, N.A. (登録日: 2022-09-05, 公開日: 2024-01-10, 最終更新日: 2024-10-23)

主引用文献

Wilkinson, M.,Xu, Y.,Thacker, D.,Taylor, A.I.P.,Fisher, D.G.,Gallardo, R.U.,Radford, S.E.,Ranson, N.A.
Structural evolution of fibril polymorphs during amyloid assembly.
Cell, 186:5798-5811.e26, 2023

PubMed Abstract: Cryoelectron microscopy (cryo-EM) has provided unprecedented insights into amyloid fibril structures, including those associated with disease. However, these structures represent the endpoints of long assembly processes, and their relationship to fibrils formed early in assembly is unknown. Consequently, whether different fibril architectures, with potentially different pathological properties, form during assembly remains unknown. Here, we used cryo-EM to determine structures of amyloid fibrils at different times during in vitro fibrillation of a disease-related variant of human islet amyloid polypeptide (IAPP-S20G). Strikingly, the fibrils formed in the lag, growth, and plateau phases have different structures, with new forms appearing and others disappearing as fibrillation proceeds. A time course with wild-type hIAPP also shows fibrils changing with time, suggesting that this is a general property of IAPP amyloid assembly. The observation of transiently populated fibril structures has implications for understanding amyloid assembly mechanisms with potential new insights into amyloid progression in disease.

PubMed: 38134875
DOI: 10.1016/j.cell.2023.11.025

実験手法

ELECTRON MICROSCOPY (3.4 Å)