Nucleation Process of a Fibril Precursor in the C-Terminal Segment of Amyloid-β

被引：49

作者：

Baftizadeh, Fahimeh ^{[1
]}

Pietrucci, Fabio ^{[2
]}

Biarnes, Xevi ^{[3
]}

Laio, Alessandro ^{[1
]}

机构：

[1] SISSA, I-34136 Trieste, Italy

[2] Ecole Polytech Fed Lausanne, Inst Theoret Phys, CH-1015 Lausanne, Switzerland

[3] URL, Biochem Lab, IQS, Barcelona 08017, Spain

来源：

PHYSICAL REVIEW LETTERS | 2013年 / 110卷 / 16期

关键词：

MOLECULAR-DYNAMICS SIMULATIONS; MONTE-CARLO SIMULATIONS; ALZHEIMERS-DISEASE; PEPTIDE; AGGREGATION; OLIGOMERS; STATE; CONFORMATIONS; A-BETA(16-22); MECHANISM;

D O I：

10.1103/PhysRevLett.110.168103

中图分类号：

O4 [物理学];

学科分类号：

0702 ;

摘要：

By extended atomistic simulations in explicit solvent and bias-exchange metadynamics, we study the aggregation process of 18 chains of the C-terminal segment of amyloid-beta, an intrinsically disordered protein involved in Alzheimer's disease and prone to form fibrils. Starting from a disordered aggregate, we are able to observe the formation of an ordered nucleus rich in beta sheets. The rate limiting step in the nucleation pathway involves crossing a barrier of approximately 40 kcal/mol and is associated with the formation of a very specific interdigitation of the side chains belonging to different sheets. This structural pattern is different from the one observed experimentally in a microcrystal of the same system, indicating that the structure of a "nascent'' fibril may differ from the one of an "extended'' fibril. DOI: 10.1103/PhysRevLett.110.168103

引用

页数：5

共 39 条

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