Multiple quantum solid-state NMR indicates a parallel, not antiparallel, organization of β-sheets in Alzheimer's β-amyloid fibrils
Multiple quantum solid-state NMR indicates a parallel, not antiparallel, organization of β-sheets in Alzheimer's β-amyloid fibrils
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DOI：
10.1073/pnas.230315097
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发表时间：
2000-11-21
影响因子：
11.1
通讯作者：
Tycko, R
中科院分区：
文献类型：
--
作者：
Antzutkin, ON;Balbach, JJ;Tycko, R
与阿尔茨海默氏病相关的老年斑含有由39至43个残基的β-淀粉样肽形成的纤维沉积物，可能具有神经毒性作用。对定向原纤维束的X射线衍射测量已经表明阿尔茨海默氏β-淀粉样蛋白原纤维和其他淀粉样蛋白原纤维的延伸β-折叠结构，但是β-折叠的超分子组织和其他结构细节还没有很好地建立，因为淀粉样蛋白原纤维的固有非结晶、不溶性的性质。在这里，我们报告固态NMR测量，使用多量子（MQ）C-13 NMR技术，探测由全长40个残基的β-淀粉样肽形成的原纤维中的β-折叠组织（A β（1-40））尽管在最近的全长β-淀粉样蛋白原纤维的结构模型中经常假定和调用反平行β-折叠组织，MQNMR数据指示寄存器内并行组织。这项工作提供了对全长β-淀粉样蛋白原纤维的位点特异性、原子级结构限制，并将MQNMR应用于结构生物学中的一个重要问题。
Senile plaques associated with Alzheimer's disease contain deposits of fibrils formed by 39- to 43-residue beta -amyloid peptides with possible neurotoxic effects. X-ray diffraction measurements on oriented fibril bundles have indicated an extended beta -sheet structure for Alzheimer's beta -amyloid fibrils and other amyloid fibrils, but the supramolecular organization of the beta -sheets and other structural details are not well established because of the intrinsically noncrystalline, insoluble nature of amyloid fibrils, Here we report solid-state NMR measurements, using a multiple quantum (MQ)C-13 NMR technique, that probe the beta -sheet organization in fibrils formed by the full-length, 40-residue beta -amyloid peptide (A beta (1-40)) Although an antiparallel beta -sheet organization often is assumed and is invoked in recent structural models for full-length beta -amyloid fibrils, the MQNMR data indicate an in-register, parallel organization. This work provides site-specific, atomic-level structural constraints on full-length beta -amyloid fibrils and applies MQNMR to a significant problem in structural biology.