8SBD

Cryo-EM structure of insulin amyloid-like fibril that is composed of two antiparallel protofilaments

8SBD の概要

• エントリーDOI: 10.2210/pdb8sbd/pdb
• EMDBエントリー: 40305
• 分子名称: Insulin B chain, Insulin A chain (2 entities in total)
• 機能のキーワード: amyloid-like fibril, signaling protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 32
• 化学式量合計: 93082.42

構造登録者

Wang, L.W.,Hall, C.,Uchikawa, E.,Chen, D.L.,Choi, E.,Zhang, X.W.,Bai, X.C. (登録日: 2023-04-03, 公開日: 2023-08-30, 最終更新日: 2025-06-04)

主引用文献

Wang, L.,Hall, C.E.,Uchikawa, E.,Chen, D.,Choi, E.,Zhang, X.,Bai, X.C.
Structural basis of insulin fibrillation.
Sci Adv, 9:eadi1057-eadi1057, 2023

PubMed Abstract: Insulin is a hormone responsible for maintaining normal glucose levels by activating insulin receptor (IR) and is the primary treatment for diabetes. However, insulin is prone to unfolding and forming cross-β fibers. Fibrillation complicates insulin storage and therapeutic application. Molecular details of insulin fibrillation remain unclear, hindering efforts to prevent fibrillation process. Here, we characterized insulin fibrils using cryo-electron microscopy (cryo-EM), showing multiple forms that contain one or more of the protofilaments containing both the A and B chains of insulin linked by disulfide bonds. We solved the cryo-EM structure of one of the fibril forms composed of two protofilaments at 3.2-Å resolution, which reveals both the β sheet conformation of the protofilament and the packing interaction between them that underlie the fibrillation. On the basis of this structure, we designed several insulin mutants that display reduced fibrillation while maintaining native IR signaling activity. These designed insulin analogs may be developed into more effective therapeutics for type 1 diabetes.

PubMed: 37713485
DOI: 10.1126/sciadv.adi1057

実験手法

ELECTRON MICROSCOPY (3.2 Å)