Cell membrane translocation of the N-terminal (1–28) part of the prion protein

• Published in: Biochemical and biophysical research communications 2002-11, Vol.299 (1), p.85-90
• Main Authors: Lundberg, P, Magzoub, M, Lindberg, M, Hällbrink, M, Jarvet, J, Eriksson, L.E.G, Langel, Ü, Gräslund, A
• Format: Article
• Language: English
• Subjects: Aggregation; Amino Acid Sequence; Animals; beta-structure; Cell Membrane - metabolism; Cell penetrating peptide; Circular Dichroism; Magnetic Resonance Spectroscopy; Membrane interaction; Mice; Microscopy, Confocal; Molecular Sequence Data; Peptide Biosynthesis; Peptides - chemistry; Prion protein N-terminus; Prions - chemistry; Prions - metabolism; Protein Sorting Signals; Protein Structure, Secondary; Protein Structure, Tertiary; Protein Transport; PrPSc Proteins - metabolism; Time Factors; Tumor Cells, Cultured; β-Structure
• ISSN: 0006-291X; 1090-2104; 1090-2104
• DOI: 10.1016/S0006-291X(02)02595-0

The N-terminal (1–28) part of the mouse prion protein (PrP) is a cell penetrating peptide, capable of transporting large hydrophilic cargoes through a cell membrane. Confocal fluorescence microscopy shows that it transports the protein avidin (67 kDa) into several cell lines. The (1–28) peptide has a strong tendency for aggregation and β-structure formation, particularly in interaction with negatively charged phospholipid membranes. The findings have implications for how prion proteins with uncleaved signal peptides in the N-termini may enter into cells, which is important for infection. The secondary structure conversion into β-structure may be relevant as a seed for the conversion into the scrapie (PrP Sc) form of the protein and its amyloidic transformation.