Manual and automatic assignment of two different Aβ40 amyloid fibril polymorphs using MAS solid-state NMR spectroscopy

IF 0.8 4区生物学 Q4 BIOPHYSICS

Biomolecular NMR Assignments Pub Date : 2024-08-09 DOI:10.1007/s12104-024-10189-z

Natalia Rodina, Riddhiman Sarkar, Dimitrios Tsakalos, Saba Suladze, Zheng Niu, Bernd Reif

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Abstract

Amyloid fibrils from Alzheimer’s amyloid-beta peptides (Aβ) are found to be polymorphic. So far, 14 Aβ40 fibril structures have been determined. The mechanism of why one particular protein sequence adopts so many different three-dimensional structures is yet not understood. In this work, we describe the assignment of the NMR chemical shifts of two Alzheimer’s disease fibril polymorphs, P1 and P2, which are formed by the amyloid-beta peptide Aβ40. The assignment is based on ¹³C-detected 3D NCACX and NCOCX experiments MAS solid-state NMR experiments. The fibril samples are prepared using an extensive seeding protocol in the absence and presence of the small heat shock protein αB-crystallin. In addition to manual assignments, we obtain chemical shift assignments using the automation software ARTINA. We present an analysis of the secondary chemical shifts and a discussion on the differences between the manual and automated assignment strategies.

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利用 MAS 固态 NMR 光谱手动和自动分配两种不同的 Aβ40 淀粉样蛋白纤维多态性。

研究发现，阿尔茨海默氏症淀粉样β肽（Aβ）的淀粉样纤维具有多态性。迄今为止，已确定了 14 种 Aβ40 纤维结构。对于一个特定的蛋白质序列为何会采用如此多不同的三维结构，人们尚未弄清其机理。在这项研究中，我们描述了由淀粉样β肽 Aβ40 形成的两种阿尔茨海默氏症纤维多态 P1 和 P2 的核磁共振化学位移的分配。这一分配基于 13C 检测到的三维 NCACX 和 NCOCX 实验 MAS 固态 NMR 实验。纤维样品是在没有和有小型热休克蛋白αB-结晶素的情况下通过广泛的播种方案制备的。除了人工赋值外，我们还使用自动化软件 ARTINA 获得了化学位移赋值。我们对二次化学位移进行了分析，并讨论了手动和自动分配策略之间的差异。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Biomolecular NMR Assignments 生物-光谱学

CiteScore

1.70

自引率

11.10%

发文量

审稿时长

6-12 weeks

期刊介绍： Biomolecular NMR Assignments provides a forum for publishing sequence-specific resonance assignments for proteins and nucleic acids as Assignment Notes. Chemical shifts for NMR-active nuclei in macromolecules contain detailed information on molecular conformation and properties. Publication of resonance assignments in Biomolecular NMR Assignments ensures that these data are deposited into a public database at BioMagResBank (BMRB; http://www.bmrb.wisc.edu/), where they are available to other researchers. Coverage includes proteins and nucleic acids; Assignment Notes are processed for rapid online publication and are published in biannual online editions in June and December.