Protein Engineering vol. 16 no. 12 pp. 861-863, 2003
© 2003 Oxford University Press
COMMUNICATION |
Similarity between the C-terminal domain of the prion protein and chimpanzee cytomegalovirus glycoprotein UL9
Department of Biomathematical Sciences, Mount Sinai School of Medicine, Box 1023, One Gustave L. Levy Place, New York, NY 10029, USA
1 To whom correspondence should be addressed at: Department of Molecular Biosciences, 2034 Haworth Hall, 1200 Sunnyside Avenue, The University of Kansas, Lawrence, KS 66045, USA. e-mail: igor{at}ku.edu
Prion diseases are a group of fatal neurodegenerative disorders associated with structural conversion of a normal, mostly 
-helical cellular prion protein, PrPC, into a pathogenic ß-sheet-rich conformation, PrPSc. The structure of PrPC is well studied, whereas the insolubility of PrPSc 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 ß-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 PrPSc. 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-ß fold to UL9. Owing to the observed sequence similarity with PrP and a putative mainly-ß fold, the UL9 glycoprotein may represent a potential target for experimental structure determination aimed at obtaining a structural template for PrPSc modeling.
Received September 2, 2003; accepted September 12, 2003