Department of Chemistry and Biochemistry; UCLA-DOE Institute for Genomics and Proteomics; STROBE, NSF Science and Technology Center, University of California, Los Angeles, Los Angeles, CA, USA.
Department of Biological Chemistry and Department of Chemistry and Biochemistry, UCLA-DOE Institute for Genomics and Proteomics, Howard Hughes Medical Institute, University of California Los Angeles, Los Angeles, CA, USA.
Nat Struct Mol Biol. 2020 May;27(5):417-423. doi: 10.1038/s41594-020-0403-y. Epub 2020 Apr 13.
Self-templating assemblies of the human prion protein are clinically associated with transmissible spongiform encephalopathies. Here we present the cryo-EM structure of a denaturant- and protease-resistant fibril formed in vitro spontaneously by a 9.7-kDa unglycosylated fragment of the human prion protein. This human prion fibril contains two protofilaments intertwined with screw symmetry and linked by a tightly packed hydrophobic interface. Each protofilament consists of an extended beta arch formed by residues 106 to 145 of the prion protein, a hydrophobic and highly fibrillogenic disease-associated segment. Such structures of prion polymorphs serve as blueprints on which to evaluate the potential impact of sequence variants on prion disease.
朊病毒蛋白的自模板组装与可传播海绵状脑病在临床上有关。在这里，我们展示了一种在体外自发形成的变性剂和蛋白酶抗性纤维的冷冻电镜结构，它由人类朊病毒蛋白的 9.7kDa 非糖基化片段组成。这种人类朊病毒纤维包含两个原纤维，它们通过螺旋对称性相互交织，并通过紧密堆积的疏水性界面连接。每个原纤维由由朊病毒蛋白的 106 到 145 位残基形成的伸展β拱组成，这是一个疏水性和高度纤维原性的疾病相关片段。这些朊病毒多态体的结构可以作为蓝图，评估序列变异对朊病毒病的潜在影响。
