Amyloid structure determination in RELION-3.1
Amyloid structure determination in RELION-3.1
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DOI：
10.1107/s2059798319016577
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发表时间：
2020-02-01
影响因子：
2.2
通讯作者：
Scheres, Sjors H. W.
中科院分区：
文献类型：
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作者：
Scheres, Sjors H. W.
ReliOn中的螺旋重建越来越多地被用于从电子冷冻显微镜(Cryo-EM)图像中确定淀粉样细丝的原子结构。然而，由于淀粉样蛋白精化的能量格局通常充满了局部最优，因此淀粉样蛋白结构的确定通常是困难的。本文旨在帮助ReliOn用户在这一过程中。它讨论了与淀粉样蛋白特别相关的螺旋重建问题，阐述了细化过程中的局部最优问题以及如何检测这些问题，并介绍了一种从无参考的2D类平均计算3D初始模型的新方法。通过提供更接近全局最优的起始模型，该方法使淀粉样蛋白结构的确定变得更容易。所描述的所有方法都是开源的，并在ReliOn-3.1中分发。使用一组公开可用的数据说明了它们的用途，这些数据来自阿尔茨海默病患者的大脑。
Helical reconstruction in RELION is increasingly being used to determine the atomic structures of amyloid filaments from electron cryo-microscopy (cryo-EM) images. However, because the energy landscape of amyloid refinements is typically fraught with local optima, amyloid structure determination is often difficult. This paper aims to help RELION users in this process. It discusses aspects of helical reconstruction that are particularly relevant to amyloids, it illustrates the problem of local optima in refinement and how to detect them, and it introduces a new method to calculate 3D initial models from reference-free 2D class averages. By providing starting models that are closer to the global optimum, this method makes amyloid structure determination easier. All methods described are open-source and distributed within RELION-3.1. Their use is illustrated using a publicly available data set on tau filaments from the brain of an individual with Alzheimer's disease.