Sanghera, Narinder, Correia, Bruno E.F.S., Correia, Joana R.S. , Ludwig, Christian, Agarwal, Sonya, Nakamura, Hironori K., Kuwata, Kazuo, Samain, Eric, Gill, Andrew, Bonev, Boyan B. and Pinheiro, Teresa J.T. (2011) Deciphering the Molecular Details for the Binding of the Prion Protein to Main Ganglioside GM1 of Neuronal Membranes. Chemistry & Biology, 18 (11). pp. 1422-1431. ISSN 1074-5521
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Item Type: | Article |
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Item Status: | Live Archive |
Abstract
The prion protein (PrP) resides in lipid rafts in vivo, and lipids modulate misfolding of the protein to infectious isoforms. Here we demonstrate that binding of recombinant PrP to model raft membranes requires the presence of ganglioside GM1. A combination of liquid- and solid-state NMR revealed the binding sites of PrP to the saccharide head group of GM1. The binding epitope for GM1 was mapped to the folded C-terminal domain of PrP, and docking simulations identified key residues in the C-terminal region of helix C and the loop between strand S2 and helix B. Crucially, this region of PrP is linked to prion resistance in vivo, and structural changes caused by lipid binding in this region may explain the requirement for lipids in the generation of infectious prions in vitro.
Additional Information: | The final published version of this article can be accessed online at https://www.sciencedirect.com/science/article/pii/S1074552111003450?via%3Dihub |
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Keywords: | prion, gm1, lipid raft |
Subjects: | C Biological Sciences > C770 Biophysical Science C Biological Sciences > C130 Cell Biology C Biological Sciences > C760 Biomolecular Science |
Divisions: | College of Science |
ID Code: | 29472 |
Deposited On: | 30 Aug 2018 14:03 |
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