Predicted secondary structure and membrane topology of the scrapie prion protein.
The integral membrane sialoglycoprotein PrPSc is the only identifiable component of the scrapie prion. Scrapie in animals and Creutzfeldt-Jakob disease in humans are transmissible, degenerative neurological diseases caused by prions. Standard predictive strategies have been used to analyze the secondary structure of the prion protein in conjunction with Fourier analysis of the primary sequence hydrophobicities to detect potential amphipathic regions. Several hydrophobic segments, a proline- and glycine-rich repeat region and putative glycosylation sites are incorporated into a model for the integral membrane topology of PrP. The complete amino acid sequences of the hamster, human and mouse prion proteins are compared and the effects of residue substitutions upon the predicted conformation of the polypeptide chain are discussed. While PrP has a unique primary structure, its predicted secondary structure shares some interesting features with the serum amyloid A proteins. These proteins undergo a post-translational modification to yield amyloid A, molecules that share with PrP the ability to polymerize into birefringent filaments. Our analyses may explain some experimental observations on PrP, and suggest further studies on the properties of the scrapie and cellular PrP isoforms.
Bazan
J F
JF
Department of Biophysics, University of California, Berkeley 94720.
Fletterick
R J
RJ
McKinley
M P
MP
Prusiner
S B
SB
D000595:Amino Acid Sequence; D001483:Base Sequence; D004247:DNA / Q000235:genetics; D007425:Intracellular Membranes / Q000378:metabolism; D008969:Molecular Sequence Data; D018620:PrPSc Proteins; D011328:Prions / Q000235:genetics; D011487:Protein Conformation; D015202:Protein Engineering; D021382:Protein Sorting Signals / Q000235:genetics; D000685:Serum Amyloid A Protein; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism
D018620:PrPSc Proteins; D011328:Prions; D021382:Protein Sorting Signals; D000685:Serum Amyloid A Protein; D014764:Viral Proteins; D004247:DNA