8ANG

Structure of the amyloid-forming peptide LYIQWL from Tc5b, grown from 30% ethanol

8ANG の概要

• エントリーDOI: 10.2210/pdb8ang/pdb
• 分子名称: Peptide LYIQWL from Tc5b, ETHANOL (2 entities in total)
• 機能のキーワード: amyloid, protein fibril
• 由来する生物種: synthetic construct
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 881.07

構造登録者

Durvanger, Z. (登録日: 2022-08-05, 公開日: 2023-08-02, 最終更新日: 2024-06-19)

主引用文献

Horvath, D.,Durvanger, Z.,K Menyhard, D.,Sulyok-Eiler, M.,Bencs, F.,Gyulai, G.,Horvath, P.,Taricska, N.,Perczel, A.
Polymorphic amyloid nanostructures of hormone peptides involved in glucose homeostasis display reversible amyloid formation.
Nat Commun, 14:4621-4621, 2023

PubMed Abstract: A large group of hormones are stored as amyloid fibrils in acidic secretion vesicles before they are released into the bloodstream and readopt their functional state. Here, we identify an evolutionarily conserved hexapeptide sequence as the major aggregation-prone region (APR) of gastrointestinal peptides of the glucagon family: xFxxWL. We determine nine polymorphic crystal structures of the APR segments of glucagon-like peptides 1 and 2, and exendin and its derivatives. We follow amyloid formation by CD, FTIR, ThT assays, and AFM. We propose that the pH-dependent changes of the protonation states of glutamate/aspartate residues of APRs initiate switching between the amyloid and the folded, monomeric forms of the hormones. We find that pH sensitivity diminishes in the absence of acidic gatekeepers and amyloid formation progresses over a broad pH range. Our results highlight the dual role of short aggregation core motifs in reversible amyloid formation and receptor binding.

PubMed: 37528104
DOI: 10.1038/s41467-023-40294-x

実験手法

X-RAY DIFFRACTION (1.5 Å)