Research Technologies Branch, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, 59840, USA.
Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
Nat Commun. 2022 Jul 13;13(1):4005. doi: 10.1038/s41467-022-30458-6.
Little is known about the structural basis of prion strains. Here we provide a high (3.0 Å) resolution cryo-electron microscopy-based structure of infectious brain-derived fibrils of the mouse anchorless RML scrapie strain which, like the recently determined hamster 263K strain, has a parallel in-register β-sheet-based core. Several structural motifs are shared between these ex vivo prion strains, including an amino-proximal steric zipper and three β-arches. However, detailed comparisons reveal variations in these shared structural topologies and other features. Unlike 263K and wildtype RML prions, the anchorless RML prions lack glycophosphatidylinositol anchors and are severely deficient in N-linked glycans. Nonetheless, the similarity of our anchorless RML structure to one reported for wildtype RML prion fibrils in an accompanying paper indicates that these post-translational modifications do not substantially alter the amyloid core conformation. This work demonstrates both common and divergent structural features of prion strains at the near-atomic level.
关于朊病毒株的结构基础知之甚少。在这里，我们提供了一个高分辨率（3.0Å）的冷冻电子显微镜结构，该结构基于传染性脑源性纤维的鼠无锚定 RML 瘙痒菌株，与最近确定的仓鼠 263K 菌株一样，具有平行的、有规律的β-片层核心。这些体外朊病毒株之间有几个结构基序共享，包括氨基近端的空间拉链和三个β拱。然而，详细比较显示这些共享的结构拓扑和其他特征存在差异。与 263K 和野生型 RML 朊病毒不同，无锚定 RML 朊病毒缺乏糖磷脂酰肌醇锚和严重缺乏 N-连接聚糖。尽管如此，我们的无锚定 RML 结构与一篇伴随论文中报告的野生型 RML 朊病毒纤维的结构相似表明，这些翻译后修饰不会显著改变淀粉样核心构象。这项工作在近原子水平上展示了朊病毒株的共同和不同的结构特征。
