8GZ8

Cryo-EM structure of Abeta2 fibril polymorph1

8GZ8 の概要

• エントリーDOI: 10.2210/pdb8gz8/pdb
• EMDBエントリー: 34392
• 分子名称: peptide self-assembled antimicrobial fibrils (2 entities in total)
• 機能のキーワード: antimicrobial fibrils, amyloid, antimicrobial protein
• 由来する生物種: Homo sapiens
• タンパク質・核酸の鎖数: 52
• 化学式量合計: 56333.99

構造登録者

Xia, W.C.,Zhang, M.M.,Liu, C. (登録日: 2022-09-26, 公開日: 2023-09-20, 最終更新日: 2024-05-22)

主引用文献

Wang, F.,Xia, W.,Zhang, M.,Wu, R.,Song, X.,Hao, Y.,Feng, Y.,Zhang, L.,Li, D.,Kang, W.,Liu, C.,Liu, L.
Engineering of antimicrobial peptide fibrils with feedback degradation of bacterial-secreted enzymes.
Chem Sci, 14:10914-10924, 2023

PubMed Abstract: Proteins and peptides can assemble into functional amyloid fibrils with distinct architectures. These amyloid fibrils can fulfil various biological functions in living organisms, and then be degraded. By incorporating an amyloidogenic segment and enzyme-cleavage segment together, we designed a peptide (enzyme-cleavage amyloid peptides (EAP))-based functional fibril which could be degraded specifically by gelatinase. To gain molecular insights into the assembly and degradation of EAP fibrils, we determined the atomic structure of the EAP fibril using cryo-electron microscopy. The amyloidogenic segment of EAP adopted a β-strand conformation and mediated EAP-fibril formation mainly steric zipper-like interactions. The enzyme-cleavage segment was partially involved in self-assembly, but also exhibited high flexibility in the fibril structure, with accessibility to gelatinase binding and degradation. Moreover, we applied the EAP fibril as a tunable scaffold for developing degradable self-assembled antimicrobial fibrils (SANs) by integrating melittin and EAP together. SANs exhibited superior activity for killing bacteria, and significantly improved the stability and biocompatibility of melittin. SANs were eliminated automatically by the gelatinase secreted from targeted bacteria. Our work provides a new strategy for rational design of functional fibrils with a feedback regulatory loop for optimizing the biocompatibility and biosafety of designed fibrils. Our work may aid further developments of "smart" peptide-based biomaterials for biomedical applications.

PubMed: 37829030
DOI: 10.1039/d3sc01089a

実験手法

ELECTRON MICROSCOPY (2.35 Å)