文章基本信息

标题：Structural studies of the scrapie prion protein by electron crystallography
本地全文：下载
作者：Holger Wille ; Melissa D. Michelitsch ; Vincent Guénebaut 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2002
卷号：99
期号：6
页码：3563-3568
DOI：10.1073/pnas.052703499
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Because the insolubility of the scrapie prion protein (PrPSc) has frustrated structural studies by x-ray crystallography or NMR spectroscopy, we used electron crystallography to characterize the structure of two infectious variants of the prion protein. Isomorphous two-dimensional crystals of the N-terminally truncated PrPSc (PrP 27-30) and a miniprion (PrPSc106) were identified by negative stain electron microscopy. Image processing allowed the extraction of limited structural information to 7 A resolution. By comparing projection maps of PrP 27-30 and PrPSc106, we visualized the 36-residue internal deletion of the miniprion and localized the N-linked sugars. The dimensions of the monomer and the locations of the deleted segment and sugars were used as constraints in the construction of models for PrPSc. Only models featuring parallel {beta}-helices as the key element could satisfy the constraints. These low-resolution projection maps and models have implications for understanding prion propagation and the pathogenesis of neurodegeneration.
关键词：electron microscopy‖image processing‖Nanogold labeling‖parallel β-helix‖amyloid structure