Biosensing of lipid-prion interactions: insights on charge effect, Cu(II)-ions binding and prion oligomerization.
The molecular mechanism involved in early stages of prion protein (PrP) conversion has been investigated using the chip based SPR technology, focusing on PrP interactions with membranes, either in its monomeric, oligomeric or Cu(II)-ions bound forms. We observed a strong interaction between PrP and cell membrane models of different lipid compositions. Circular dichroism tests show that membrane-bound, oligomerized or Cu(II)-complexed PrP may adopt a β-sheet-rich conformation. Moreover, upon PrP binding membrane vesicles may aggregate and/or be fragmented depending on vesicle net-charge and their lipid/raft composition. The whole study emphasizes the outstanding performance of the on-a-chip approach for the investigation of prion conversion and could be useful for developing sensor formats for prion assessments in biological samples.
Steunou
Stéphanie
S
Virologie et Immunologie Moléculaires, Institut National de la Recherche Agronomique, 78350 Jouy en Josas, France.
Chich
Jean-François
JF
Rezaei
Human
H
Vidic
Jasmina
J
D000818:Animals; D015374:Biosensing Techniques / Q000379:methods*; D002942:Circular Dichroism; D003300:Copper / Q000737:chemistry; D014644:Genetic Variation; D066298:In Vitro Techniques; D008027:Light; D008081:Liposomes; D008563:Membrane Lipids / Q000737:chemistry; D021962:Membrane Microdomains / Q000737:chemistry; D046529:Microscopy, Electron, Transmission; D011328:Prions / Q000737:chemistry* / Q000235:genetics / Q000648:ultrastructure; D011485:Protein Binding; D055503:Protein Multimerization; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000648:ultrastructure; D012542:Scattering, Radiation; D012756:Sheep; D020349:Surface Plasmon Resonance
D008081:Liposomes; D008563:Membrane Lipids; D011328:Prions; D011994:Recombinant Proteins; D003300:Copper