8QWV

Structure of the amyloid-forming peptide LYIQNL, grown in the presence of ethanol

8QWV の概要

• エントリーDOI: 10.2210/pdb8qwv/pdb
• 分子名称: Peptide LYIQNL, ETHANOL (3 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: 2
• 化学式量合計: 1617.92

構造登録者

Durvanger, Z. (登録日: 2023-10-20, 公開日: 2024-08-07, 最終更新日: 2024-09-04)

主引用文献

Durvanger, Z.,Bencs, F.,Menyhard, D.K.,Horvath, D.,Perczel, A.
Solvent induced amyloid polymorphism and the uncovering of the elusive class 3 amyloid topology.
Commun Biol, 7:968-968, 2024

PubMed Abstract: Aggregation-prone-motifs (APRs) of proteins are short segments, which - as isolated peptides - form diverse amyloid-like crystals. We introduce two APRs - designed variants of the incretin mimetic Exendin-4 - that both display crystal-phase polymorphism. Crystallographic and spectroscopic analysis revealed that a single amino-acid substitution can greatly reduce topological variability: while LYIQWL can form both parallel and anti-parallel β-sheets, LYIQNL selects only the former. We also found that the parallel/anti-parallel switch of LYIQWL can be induced by simply changing the crystallization temperature. One crystal form of LYIQNL was found to belong to the class 3 topology, an arrangement previously not encountered among proteinogenic systems. We also show that subtle environmental changes lead to crystalline assemblies with different topologies, but similar interfaces. Spectroscopic measurements showed that polymorphism is already apparent in the solution state. Our results suggest that the temperature-, sequence- and environmental sensitivity of physiological amyloids is reflected in assemblies of the APR segments, which, complete with the new class 3 crystal form, effectively sample all the originally proposed basic topologies of amyloid-like aggregates.

PubMed: 39122990
DOI: 10.1038/s42003-024-06621-8

実験手法

X-RAY DIFFRACTION (1.7 Å)