期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 277, 期 24, 页码 21140-21148出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M111402200
关键词
-
In vivo under pathological conditions, the normal cellular form of the prion protein, PrPC (residues 23-231), misfolds to the pathogenic isoform PrPSc, a beta-rich aggregated pathogenic multimer. Proteinase K digestion of PrPSc leads to a proteolytically resistant core, PrP 27-30 (residues 90-231), that can form amyloid fibrils. To study the kinetic pathways of amyloid formation in vitro, we used unglycosylated recombinant PrP corresponding to the proteinase K-resistant core of PrPSc and found that it can adopt two non-native abnormal isoforms, a beta-oligomer and an amyloid fibril. Several lines of kinetic data suggest that the beta-oligomer is not on the pathway to amyloid formation. The preferences for forming either a beta-oligomer or amyloid can be dictated by experimental conditions, with acidic pH similar to that seen in endocytic vesicles favoring the beta-oligomer and neutral pH favoring amyloid. Although both abnormal isoforms have high beta-sheet content and bind 1-anilinonaphthalene-8-sulfonate, they are dissimilar structurally. Multiple pathways of misfolding and the formation of distinct beta-sheet-rich abnormal isoforms may explain the difficulties in refolding PrPSc in vitro, the need for a PrPSc template, and the significant variation in disease presentation and neuropathology.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据