8XWG

OspA variants for thioflavin-T binding

8XWG の概要

• エントリーDOI: 10.2210/pdb8xwg/pdb
• 分子名称: Outer Surface Protein A (2 entities in total)
• 機能のキーワード: beta-sheet, thioflavin-t, amyloid, unknown function
• 由来する生物種: Borreliella burgdorferi (Lyme disease spirochete)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 34488.41

構造登録者

Makabe, K.,Miura, Y. (登録日: 2024-01-16, 公開日: 2024-11-27)

主引用文献

Miura, Y.,Namioka, S.,Iwai, A.,Yoshida, N.,Konno, H.,Sohma, Y.,Kanai, M.,Makabe, K.
Redesign of a thioflavin-T-binding protein with a flat beta-sheet to evaluate a thioflavin-T-derived photocatalyst with enhanced affinity.
Int.J.Biol.Macromol., 269:131992-131992, 2024

PubMed Abstract: Amyloids, proteinous aggregates with β-sheet-rich fibrils, are involved in several neurodegenerative diseases such as Alzheimer's disease; thus, their detection is critically important. The most common fluorescent dye for amyloid detection is thioflavin-T (ThT), which shows on/off fluorescence upon amyloid binding. We previously reported that an engineered globular protein with a flat β-sheet, peptide self-assembly mimic (PSAM), can be used as an amyloid binding model. In this study, we further explored the residue-specific properties of ThT-binding to the flat β-sheet by introducing systematic mutations. We found that site-specific mutations at the ThT-binding channel enhanced affinity. We also evaluated the binding of a ThT-based photocatalyst, which showed the photooxygenation activity on the amyloid fibril upon light radiation. Upon binding of the photocatalyst to the PSAM variant, singlet oxygen-generating activity was observed. The results of this study expand our understanding of the detailed binding mechanism of amyloid-specific molecules.

PubMed: 38697433
DOI: 10.1016/j.ijbiomac.2024.131992

実験手法

X-RAY DIFFRACTION (2 Å)