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标题：Structural plasticity of the cellular prion protein and implications in health and disease
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作者：Barbara Christen ; Fred F. Damberger ; Daniel R. Pérez 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：2013
卷号：110
期号：21
页码：8549-8554
DOI：10.1073/pnas.1306178110
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Two lines of transgenic mice expressing mouse/elk and mouse/horse prion protein (PrP) hybrids, which both form a well-structured {beta}2-2 loop in the NMR structures at 20 {degrees}C termed rigid-loop cellular prion proteins (RL-PrPC), presented with accumulation of the aggregated scrapie form of PrP in brain tissue, and the mouse/elk hybrid has also been shown to develop a spontaneous transmissible spongiform encephalopathy. Independently, there is in vitro evidence for correlations between the amino acid sequence in the {beta}2-2 loop and the propensity for conformational transitions to disease-related forms of PrP. To further contribute to the structural basis for these observations, this paper presents a detailed characterization of RL-PrPC conformations in solution. A dynamic local conformational polymorphism involving the {beta}2-2 loop was found to be evolutionarily preserved among all mammalian species, including those species for which the WT PrP forms an RL-PrPC. The interconversion between two ensembles of PrPC conformers that contain, respectively, a 310-helix turn or a type I {beta}-turn structure of the {beta}2-2 loop, exposes two different surface epitopes, which are analyzed for their possible roles in the still evasive function of PrPC in healthy organisms and/or at the onset of a transmissible spongiform encephalopathy.
关键词：prion protein stability ; protein dynamics ; conformational equilibrium ; NMR line shape analysis