Prion protein structure is affected by pH-dependent interaction with membranes: a study in a model system.
Interaction of full length recombinant hamster prion protein with liposomes mimicking lipid rafts or non-raft membrane regions was studied by circular dichroism, chemical cross-linking and sucrose gradient ultracentrifugation. At pH 7.0, the protein bound palmitoyloleoylphosphatidylcholine/cholesterol/sphingomyelin/monosialoganglioside GM1 (GM1) ganglioside liposomes but not palmitoyloleoylphosphatidylcholine alone (bound/free=0.33 and 0.01, respectively), maintaining the native alpha-helical structure and monomeric form. At pH 5.0, though still binding to quaternary mixtures, in particular GM1, the protein bound also to palmitoyloleoylphosphatidylcholine (bound/free 0.35) becoming unfolded and oligomeric. The pH-dependent interaction with raft or non-raft membranes might have implication in vivo, by stabilizing or destabilizing the protein.
Re
Francesca
F
Department of Experimental Medicine, University of Milano-Bicocca, via Cadore 48, Monza, Italy. francesca.re@unimib.it
Sesana
Silvia
S
Barbiroli
Alberto
A
Bonomi
Francesco
F
Cazzaniga
Emanuela
E
Lonati
Elena
E
Bulbarelli
Alessandra
A
Masserini
Massimo
M
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D006224:Cricetinae; D006863:Hydrogen-Ion Concentration; D008081:Liposomes; D008958:Models, Molecular; D011328:Prions / Q000737:chemistry*; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry
D008081:Liposomes; D011328:Prions; D011994:Recombinant Proteins