6OC9

S8 phosphorylated beta amyloid 40 fibrils

6OC9 の概要

• エントリーDOI: 10.2210/pdb6oc9/pdb
• NMR情報: BMRB: 30596
• 分子名称: Amyloid-beta precursor protein, PHOSPHONATE (2 entities in total)
• 機能のキーワード: amyloid fibrils, beta amyloid, phosphorylation, post-translational modification, signaling protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 10
• 化学式量合計: 44158.32

構造登録者

Qiang, W.,Hu, Z.W. (登録日: 2019-03-22, 公開日: 2019-06-05, 最終更新日: 2024-05-01)

主引用文献

Hu, Z.W.,Vugmeyster, L.,Au, D.F.,Ostrovsky, D.,Sun, Y.,Qiang, W.
Molecular structure of an N-terminal phosphorylated beta-amyloid fibril.
Proc.Natl.Acad.Sci.USA, 116:11253-11258, 2019

PubMed Abstract: The structural polymorphism in β-amyloid (Aβ) plaques from Alzheimer disease (AD) has been recognized as an important pathological factor. Plaques from sporadic AD patients contain fibrillar deposits of various amyloid proteins/peptides, including posttranslational modified Aβ (PTM-Aβ) subtypes. Although many PTM-Aβs were shown to accelerate the fibrillation process, increase neuronal cytotoxicity of aggregates, or enhance the stability of fibrils, the contribution of PTM-Aβs to structural polymorphisms and their pathological roles remains unclear. We report here the NMR-based structure for the Ser-8-phosphorylated 40-residue Aβ (pS8-Aβ) fibrils, which shows significant difference to the wild-type fibrils, with higher cross-seeding efficiency and thermodynamic stability. Given these physicochemical properties, the structures originated from pS8-Aβ fibrils may potentially dominate the polymorphisms in the mixture of wild-type and phosphorylated Aβ deposits. Our results imply that Aβ subtypes with "seeding-prone" properties may influence the polymorphisms of amyloid plaques through the cross-seeding process.

PubMed: 31097588
DOI: 10.1073/pnas.1818530116

実験手法

SOLID-STATE NMR