6HHD

Mouse Prion Protein in complex with Nanobody 484

6HHD の概要

• エントリーDOI: 10.2210/pdb6hhd/pdb
• 分子名称: Major prion protein, Nanobody 484, CHLORIDE ION, ... (9 entities in total)
• 機能のキーワード: prion, nanobody, aggregation, b-sheet, protein binding
• 由来する生物種: Mus musculus (House Mouse); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 53055.00

構造登録者

Soror, S.,Abskharon, R.,Wohlkonig, A. (登録日: 2018-08-28, 公開日: 2019-12-11, 最終更新日: 2024-11-13)

主引用文献

Abskharon, R.,Wang, F.,Wohlkonig, A.,Ruan, J.,Soror, S.,Giachin, G.,Pardon, E.,Zou, W.,Legname, G.,Ma, J.,Steyaert, J.
Structural evidence for the critical role of the prion protein hydrophobic region in forming an infectious prion.
Plos Pathog., 15:e1008139-e1008139, 2019

PubMed Abstract: Prion or PrPSc is the proteinaceous infectious agent causing prion diseases in various mammalian species. Despite decades of research, the structural basis for PrPSc formation and prion infectivity remains elusive. To understand the role of the hydrophobic region in forming infectious prion at the molecular level, we report X-ray crystal structures of mouse (Mo) prion protein (PrP) (residues 89-230) in complex with a nanobody (Nb484). Using the recombinant prion propagation system, we show that the binding of Nb484 to the hydrophobic region of MoPrP efficiently inhibits the propagation of proteinase K resistant PrPSc and prion infectivity. In addition, when added to cultured mouse brain slices in high concentrations, Nb484 exhibits no neurotoxicity, which is drastically different from other neurotoxic anti-PrP antibodies, suggesting that the Nb484 can be a potential therapeutic agent against prion disease. In summary, our data provides the first structure-function evidence supporting a crucial role of the hydrophobic region of PrP in forming an infectious prion.

PubMed: 31815959
DOI: 10.1371/journal.ppat.1008139

実験手法

X-RAY DIFFRACTION (2.102 Å)