Transformation of amyloid β(1-40) oligomers into fibrils is characterized by a major change in secondary structure

被引：127

作者：

Sarroukh, Rabia ^{[1
]}

Cerf, Emilie ^{[1
]}

Derclaye, Sylvie ^{[2
]}

Dufrene, Yves F. ^{[2
]}

Goormaghtigh, Erik ^{[1
]}

Ruysschaert, Jean-Marie ^{[1
]}

Raussens, Vincent ^{[1
]}

机构：

[1] Univ Libre Bruxelles, Lab Struct & Funct Biol Membranes, Fac Sci, Ctr Struct Biol & Bioinformat, B-1050 Brussels, Belgium

[2] Catholic Univ Louvain, Unite Chim Interfaces, B-1348 Louvain, Belgium

来源：

CELLULAR AND MOLECULAR LIFE SCIENCES | 2011年 / 68卷 / 08期

关键词：

Amyloid-beta; Alzheimer's disease; Aggregation; Secondary structure changes; Infrared spectroscopy; A-BETA OLIGOMERS; INFRARED-SPECTROSCOPY; ALZHEIMERS-DISEASE; CONFORMATIONAL TRANSITION; EXPERIMENTAL CONSTRAINTS; COMMON MECHANISM; PEPTIDE; SHEET; AGGREGATION; TOXICITY;

D O I：

10.1007/s00018-010-0529-x

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Alzheimer's disease (AD) is a neurodegenerative disorder occurring in the elderly. It is widely accepted that the amyloid beta peptide (A beta) aggregation and especially the oligomeric states rather than fibrils are involved in AD onset. We used infrared spectroscopy to provide structural information on the entire aggregation pathway of A beta(1-40), starting from monomeric A beta to the end of the process, fibrils. Our structural study suggests that conversion of oligomers into fibrils results from a transition from antiparallel to parallel beta-sheet. These structural changes are described in terms of H-bonding rupture/formation, beta-strands reorientation and beta-sheet elongation. As antiparallel beta-sheet structure is also observed for other amyloidogenic proteins forming oligomers, reorganization of the beta-sheet implicating a reorientation of beta-strands could be a generic mechanism determining the kinetics of protein misfolding. Elucidation of the process driving aggregation, including structural transitions, could be essential in a search for therapies inhibiting aggregation or disrupting aggregates.

引用

页码：1429 / 1438

页数：10

共 55 条

[1] Supramolecular structure in full-length Alzheimer's β-amyloid fibrils:: Evidence for a parallel β-sheet organization from solid-state nuclear magnetic resonance [J].