9ULZ

Cryo-EM structure of hIAPP fibrils extracted from a donor with T2D and pancreatic cancer

9ULZ の概要

• エントリーDOI: 10.2210/pdb9ulz/pdb
• EMDBエントリー: 64268
• 分子名称: Islet amyloid polypeptide (1 entity in total)
• 機能のキーワード: amyloid fibrils, type ii diabetes, hiapp, 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: 46911.65

構造登録者

Cao, Q.,Liu, W.,Han, J. (登録日: 2025-04-21, 公開日: 2026-01-14)

主引用文献

Liu, W.,Han, J.,Gong, W.,Zhang, F.,Cao, Q.
Structure of pancreatic hIAPP fibrils derived from patients with type 2 diabetes.
Cell, 2026

PubMed Abstract: Type 2 diabetes (T2D) impacts the quality of life and lifespan of nearly 10% of the global population. Human islet amyloid polypeptide (hIAPP) constitutes a major component of islet amyloid deposition in patients with T2D, with hIAPP fibrils believed to play a key role in the pathogenesis of T2D. In this study, we determined the cryo-electron microscopy (cryo-EM) structure of hIAPP fibrils extracted from surgically resected pancreases of three donors with T2D. These fibrils exhibit a uniform morphology, comprising two symmetrical protofilaments encompassing residues 2-37 of hIAPP and adopting an Ω-shaped fold. The structure of pancreatic hIAPP fibrils differs from that of fibrils formed in vitro. Additional densities were observed in the pancreatic hIAPP fibrils, suggesting ligand binding that may play significant roles in the pathogenesis of T2D. Collectively, our study presents the atomic structure of pathological hIAPP fibrils, contributing to the therapeutic and mechanistic exploration of T2D.

PubMed: 41483806
DOI: 10.1016/j.cell.2025.12.001

実験手法

ELECTRON MICROSCOPY (2.9 Å)