Monomeric A-Synuclein (As) Inhibits Amyloidogenesis Of Human Prion Protein (Hprp) By Forming A Stable As-Hprp Hetero-Dimer.

Intermolecular interaction between hPrP and alpha S was investigated using high-speed atomic force microscopy, dynamic light scattering, and nuclear magnetic resonance. We found that hPrP spontaneously gathered and naturally formed oligomers. Upon addition of monomer alpha S with a disordered conformation, poly-dispersive property of hPrP was lost, and hetero-dimer formation started quite coherently, and further oligomerization was not observed. Solution structure of hPrP-alpha S dimer was firstly characterized using hetero-nuclear NMR spectroscopy. In this hetero-dimeric complex, C-terminal helical region of hPrP was in the molten-globule like state, while specific sites including hot spot and C-terminal region of alpha S selectively interacted with hPrP. Thus alpha S may suppress amyloidogenesis of hPrP by trapping the hPrP intermediate by the formation of a stable hetero-dimer with hPrP.