title: Deciphering the molecular details for the binding of the prion protein to main ganglioside GM1 of neuronal membranes.
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.
authors: School of Life Sciences, University of Warwick, Gibbet Hill Road, Coventry CV4 7AL, UK.
authors: Narinder
authors: N
authors: Sanghera
authors: Bruno E F S
authors: BE
authors: Correia
authors: Joana R S
authors: JR
authors: Correia
authors: Christian
authors: C
authors: Ludwig
authors: Sonya
authors: S
authors: Agarwal
authors: Hironori K
authors: HK
authors: Nakamura
authors: Kazuo
authors: K
authors: Kuwata
authors: Eric
authors: E
authors: Samain
authors: Andrew C
authors: AC
authors: Gill
authors: Boyan B
authors: BB
authors: Bonev
authors: Teresa J T
authors: TJ
authors: Pinheiro
mesh_terms: D001665:Binding Sites; D003198:Computer Simulation; D005677:G(M1) Ganglioside / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D021962:Membrane Microdomains / Q000378:metabolism*; D008958:Models, Molecular; D011328:Prions / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D011328:Prions; D011994:Recombinant Proteins; D005677:G(M1) Ganglioside