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Deciphering the molecular details for the binding of the prion protein to main ganglioside GM1 of neuronal membranes
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Sanghera, Narinder, Correia, Bruno E. F. S, Correia, Joana R. S., Ludwig, Christian, Agarwal, Sonya, Nakamura, Hironori K., Kuwata, Kazuo, Samain, Eric, Gill, Andrew C., 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, Vol.18 (No.11). pp. 1422-1431. doi:10.1016/j.chembiol.2011.08.016 ISSN 1074-5521.
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Official URL: http://dx.doi.org/10.1016/j.chembiol.2011.08.016
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.
| Item Type: | Journal Article | ||||
|---|---|---|---|---|---|
| Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | ||||
| Journal or Publication Title: | Chemistry & Biology | ||||
| Publisher: | Cell Press | ||||
| ISSN: | 1074-5521 | ||||
| Official Date: | 2011 | ||||
| Dates: |
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| Volume: | Vol.18 | ||||
| Number: | No.11 | ||||
| Page Range: | pp. 1422-1431 | ||||
| DOI: | 10.1016/j.chembiol.2011.08.016 | ||||
| Status: | Peer Reviewed | ||||
| Publication Status: | Published | ||||
| Access rights to Published version: | Restricted or Subscription Access | ||||
| Funder: | Biotechnology and Biological Sciences Research Council (BBSRC) | ||||
| Grant number: | 88/BS516471 BB/3510924 (BBSRC) |
Data sourced from Thomson Reuters' Web of Knowledge
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