Similarity between the C-terminal domain of the prion protein and chimpanzee cytomegalovirus glycoprotein UL9

Prion diseases are a group of fatal neurodegenerative disorders associated with structural conversion of a normal, mostly α-helical cellular prion protein, PrP^C, into a pathogenic β-sheet-rich conformation, PrP^Sc. The structure of PrP^C is well studied, whereas the insolubility of PrP^Sc makes the characterization of its structure problematic. No proteins similar to PrP, except for its paralog with the same fold, PrP-Doppel, are known. However, PrP-Doppel does not undergo a structural transition into a β-sheet-rich conformation. Structural information from proteins that share a weak but significant sequence similarity with PrP may be used to gain additional insights into the conformation of PrP^Sc. We construct a sequence profile corresponding to the structured domain of PrP and use this profile to search the SWISS-PROT and TrEMBL databases. We identify a significant sequence similarity between PrP and chimpanzee cytomegalovirus glycoprotein UL9. This glycoprotein scores higher than all PrP-Doppel sequences. Fold recognition methods assign a mainly-β fold to UL9. Owing to the observed sequence similarity with PrP and a putative mainly-β fold, the UL9 glycoprotein may represent a potential target for experimental structure determination aimed at obtaining a structural template for PrP^Sc modeling.