PROSITE documentation PDOC00263

Prion protein signatures

Prion protein (PrP) [1,2,3] is a small glycoprotein found in high quantity in the brains of humans or animals infected with a number of degenerative neurological diseases such as Kuru, Creutzfeldt-Jacob disease (CJD), scrapie or bovine spongiform encephalopathy (BSE). PrP is encoded in the host genome and expressed both in normal and infected cells. It has a tendency to aggregate yielding polymers called rods.

Structurally, PrP is a protein consisting of a signal peptide, followed by an N-terminal domain that contains tandem repeats of a short motif (PHGGGWGQ in mammals, PHNPGY in chicken), itself followed by a highly conserved domain of about 140 residues that contains a disulfide bond. Finally comes a C-terminal hydrophobic domain post-translationally removed when PrP is attached to the extracellular side of the cell membrane by a GPI-anchor. The structure of PrP is shown in the following schematic representation:

 +---+----------------+-******-------------------****-----+-----+
 |Sig| Tandem repeats |                    C        C    S|     |
 +---+----------------+--------------------|--------|----|+-----+
                                           +--------+    |
                                                         GPI

'C': conserved cysteine involved in a disulfide bond.
'*': position of the patterns.

As signature pattern for PrP, we selected a perfectly conserved alanine- and glycine-rich region of 16 residues as well as a region centered on the second cysteine involved in the disulfide bond.