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Binding of prion protein to lipid membranes and implications for prion conversion
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UNSPECIFIED (2002) Binding of prion protein to lipid membranes and implications for prion conversion. Journal of Molecular Biology, 315 (5). pp. 1241-1256. doi:10.1006/jmbi.2001.5322 ISSN 0022-2836.
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Official URL: http://dx.doi.org/10.1006/jmbi.2001.5322
Abstract
The binding of the Syrian hamster prion protein, SHaPrP(90-231), to model lipid membranes was investigated by tryptophan fluorescence. Membranes composed of negatively charged or zwitterionic lipids, and raft-like membranes containing dipalmitoylphosphatidylcholine1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), cholesterol and sphingomyelin, were investigated. It was found that SHaPrP(90-231) binds to negatively charged lipid membranes and raft-like membranes. Binding of PrP to negatively charged lipid membranes involves both electrostatic and hydrophobic lipid-protein interactions and results in partial insertion of PrP into the lipid bilayer. This membrane-inserted conformation of PrP is richer in beta-sheet structure and has a disruptive effect on the integrity of the lipid bilayer, leading to total release of vesicle contents. In contrast, the binding of PrP to raft-like membranes is driven by hydrophobic lipid-protein interactions and induces the formation of alpha-helical structure. This conformation of PrP with a high content of alpha-helix is formed only at pH 7 and does not destabilize the lipid bilayer. Our findings support the view that an interaction of PrP with lipid membranes could play a role in PrP conversion. (C) 2002 Elsevier Science Ltd.
Item Type: | Journal Article | ||||
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Subjects: | Q Science > QD Chemistry | ||||
Journal or Publication Title: | Journal of Molecular Biology | ||||
Publisher: | ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD | ||||
ISSN: | 0022-2836 | ||||
Official Date: | 1 February 2002 | ||||
Dates: |
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Volume: | 315 | ||||
Number: | 5 | ||||
Number of Pages: | 16 | ||||
Page Range: | pp. 1241-1256 | ||||
DOI: | 10.1006/jmbi.2001.5322 | ||||
Publication Status: | Published |
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