期刊
STRUCTURE
卷 21, 期 11, 页码 2061-2068出版社
CELL PRESS
DOI: 10.1016/j.str.2013.08.025
关键词
-
资金
- National Institutes of Health (NIH) MD/PhD NRSA [F30 NS646373]
- Burroughs Wellcome Fund Travel Award [1009071]
- NIH [2R01 NS046478, R01 NS071035, R01 NS060729, S10 RR029388]
The spread of misfolded proteins may occur in many neurodegenerative diseases. Mammalian prions are currently the only misfolded proteins in which high specific biological infectivity can be produced in vitro. Using a system that generates infectious prions de novo from purified recombinant PrP and conversion cofactors palmitoyl-oleoyl-phosphatidyl-glycerol (POPG) and RNA, we examined by deuterium exchange mass spectrometry (DXMS) the stepwise protein conformational changes that occur during prion formation. We found that initial incubation with POPG causes major structural changes in PrP involving all three alpha helices and one beta strand, with subsequent addition of RNA rendering the N terminus highly exposed. Final conversion into the infectious PrPSc form was accompanied by globally decreased solvent exposure, with persistence of the major cofactor-induced conformational features. Thus, we report that cofactor molecules appear to induce major structural rearrangements during prion formation, initiating a dynamic sequence of conformational changes resulting in biologically active prions.
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