7YL3

Structure of hIAPP-TF-type1

7YL3 の概要

• エントリーDOI: 10.2210/pdb7yl3/pdb
• EMDBエントリー: 33902
• 分子名称: Islet amyloid polypeptide (1 entity in total)
• 機能のキーワード: amylin, protein fibril
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 46899.83

構造登録者

Li, D.,Zhang, X.,Wang, Y.,Zhu, P. (登録日: 2022-07-25, 公開日: 2022-12-28, 最終更新日: 2024-05-08)

主引用文献

Li, D.,Zhang, X.,Wang, Y.,Zhang, H.,Song, K.,Bao, K.,Zhu, P.
A new polymorphism of human amylin fibrils with similar protofilaments and a conserved core.
Iscience, 25:105705-105705, 2022

PubMed Abstract: Pancreatic amyloid deposits composed of a fibrillar form of the human islet amyloid polypeptide (hIAPP) are the pathological hallmark of type 2 diabetes (T2D). Although various cryo-EM structures of polymorphic hIAPP fibrils were reported, the underlying polymorphic mechanism of hIAPP remains elusive. Meanwhile, the structure of hIAPP fibrils with all residues visible in the fibril core is not available. Here, we report the full-length structures of two different polymorphs of hIAPP fibrils, namely slim form (SF, dimer) and thick form (TF, tetramer), formed in a salt-free environment, which share a similar ζ-shaped protofilament but differ in inter-protofilament interfaces. In the absence of salt, electrostatic interactions were found to play a dominant role in stabilizing the fibril structure, suggesting an antagonistic effect between electrostatic and hydrophobic interactions in different salt concentrations environments. Our results shed light on understanding the mechanism of amyloid fibril polymorphism.

PubMed: 36567711
DOI: 10.1016/j.isci.2022.105705

実験手法

ELECTRON MICROSCOPY (3.2 Å)