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Binding of prion proteins to lipid membranes
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Critchley, Peter, Kazlauskaite, Jurate, Eason, Robert and Pinheiro, Teresa J. T. (2002) Binding of prion proteins to lipid membranes. Biochemical and Biophysical Research Communications, 313 (3). pp. 559-567. doi:10.1016/j.bbrc.2003.12.004 ISSN 0006-291X.
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Official URL: http://dx.doi.org/10.1016/j.bbrc.2003.12.004
Abstract
A key molecular event in prion diseases is the conversion of the normal cellular form of the prion protein (PrPC) to an aberrant form known as the scrapie isoform, PrPSc. Under normal physiological conditions PrPC is attached to the outer leaflet of the plasma membrane via a GPI-anchor. It has been proposed that a direct interaction between PrP and lipid membranes could be involved in the conversion of PrPC to its disease-associated corrupted conformation, PrPSc. Recombinant PrP can be refolded into an alpha-helical structure, designated alpha-PrP isoform, or into P-sheet-rich states, designated beta-PrP isoform. The current study investigates the binding of recombinant PrP isoforms to model lipid membranes using surface plasmon resonance spectroscopy. The binding of alpha- and beta-PrP to negatively charged lipid membranes of POPG, zwitterionic membranes of DPPC, and model raft membranes composed of DPPC, cholesterol, and sphingomyelin is compared at pH 7 and 5, to simulate the environment at the plasma membrane and within endosomes, respectively. It is found that PrP binds strongly to lipid membranes. The strength of the association of PrP with lipid membranes depends on the protein conformation and pH, and involves both hydrophobic and electrostatic lipid-protein interactions. Competition binding measurements established that the binding of alpha-PrP to lipid membranes follows a decreasing order of affinity to POPG > DPPC > rafts.
Item Type: | Journal Article | ||||
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Subjects: | Q Science > QD Chemistry Q Science > QH Natural history > QH301 Biology |
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Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | ||||
Journal or Publication Title: | Biochemical and Biophysical Research Communications | ||||
Publisher: | Elsevier | ||||
ISSN: | 0006-291X | ||||
Official Date: | 2002 | ||||
Dates: |
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Volume: | 313 | ||||
Number: | 3 | ||||
Number of Pages: | 9 | ||||
Page Range: | pp. 559-567 | ||||
DOI: | 10.1016/j.bbrc.2003.12.004 | ||||
Status: | Peer Reviewed | ||||
Publication Status: | Published |
Data sourced from Thomson Reuters' Web of Knowledge
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