9JB2

Cryo-EM structure of the type II amyloid-beta 42 fibril containing a D-Asp at positions 7 and 23

これはPDB形式変換不可エントリーです。

9JB2 の概要

• エントリーDOI: 10.2210/pdb9jb2/pdb
• EMDBエントリー: 61305
• 分子名称: Amyloid-beta precursor protein (1 entity in total)
• 機能のキーワード: aggregation, protein fibril
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 15
• 化学式量合計: 67801.31

構造登録者

Hsiao, L.C.,Lee, C.H.,Hsu, M.F.,Hsu, S.T. (登録日: 2024-08-26, 公開日: 2025-03-26, 最終更新日: 2025-04-09)

主引用文献

Hsiao, L.C.,Lee, C.H.,Mazmanian, K.,Yoshida, M.,Ito, G.,Murata, T.,Utsunomiya-Tate, N.,Haino, T.,Tate, S.I.,Hsu, S.D.
Impacts of D-aspartate on the Aggregation Kinetics and Structural Polymorphism of Amyloid beta Peptide 1-42.
J.Mol.Biol., 437:169092-169092, 2025

PubMed Abstract: Isomerization of L-Aspartate (L-Asp) into D-aspartate (D-Asp) occurs naturally in proteins at a rate that is much faster than that of other amino acid types. Accumulation of D-Asp is age-dependent, which could alter protein structures and, therefore, functions. Site-specific introduction of D-Asp can accelerate aggregation kinetics of a variety of proteins associated with misfolding diseases. Here, we showed by thioflavin T fluorescence that the isomerization of L-Asp at different positions of amyloid β peptide 1-42 (Aβ42) generates opposing effects on its aggregation kinetics. We further determined the atomic structures of Aβ42 amyloid fibrils harboring a single D-Asp at position 23 and two D-Asp at positions 7 and 23 by cryo-electron microscopy helical reconstruction - cross-validated by cryo-electron tomography and atomic force microscopy - to reveal how D-Asp contributes to the formation of a unique triple stranded amyloid fibril structure stabilized by two threads of well-ordered water molecules. These findings provide crucial insights into how the conversion from L- to D-Asp influences the aggregation propensity and amyloid polymorphism of Aβ42.

PubMed: 40090459
DOI: 10.1016/j.jmb.2025.169092

実験手法

ELECTRON MICROSCOPY (2.9 Å)