A New Structural Model of Aβ40 Fibrils

被引：269

作者：

Bertini, Ivano ^{[1
,2
,3
]}

Gonnelli, Leonardo ^{[1
]}

Luchinat, Claudio ^{[1
,2
]}

Mao, Jiafei ^{[1
,3
]}

Nesi, Antonella ^{[1
]}

机构：

[1] Univ Florence, Magnet Resonance Ctr CERM, I-50019 Sesto Fiorentino, Italy

[2] Univ Florence, Dept Chem Ugo Shiff, I-50019 Sesto Fiorentino, Italy

[3] Fdn Farmacogen FiorGen Onlus, I-50019 Sesto Fiorentino, Italy

来源：

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | 2011年 / 133卷 / 40期

关键词：

SOLID-STATE NMR; ANGLE-SPINNING NMR; BETA-AMYLOID FIBRILS; DISCRETE MOLECULAR-DYNAMICS; ALZHEIMERS-DISEASE; CROSS-POLARIZATION; EXPERIMENTAL CONSTRAINTS; MEMBRANE-PROTEINS; CHEMICAL-SHIFTS; 3D STRUCTURE;

D O I：

10.1021/ja2035859

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

The amyloid fibrils of beta-amyloid (A beta) peptides play important roles in the pathology of Alzheimer's disease. Comprehensive solid-state NMR (SSNMR) structural studies on uniformly isotope-labeled A beta assemblies have been hampered for a long time by sample heterogeneity and low spectral resolution. In this work, SSNMR studies on well-ordered fibril samples of A beta(40) with an additional N-terminal methionine provide high-resolution spectra which lead to an accurate structural model. The fibrils studied here carry distinct structural features compared to previous reports. The inter-beta-strand contacts within the U-shaped beta-strand-turn-beta-strand motif are shifted, the N-terminal region adopts a beta-conformation, and new inter-monomer contacts occur at the protofilament interface. The revealed structural diversity in A beta fibrils points to a complex picture of A beta fibrillation.

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收藏

页码：16013 / 16022

页数：10

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