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 alpha-helical cellular prion protein, PrP(C), into a pathogenic beta-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 beta-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-beta fold to UL9. Owing to the observed sequence similarity with PrP and a putative mainly-beta fold, the UL9 glycoprotein may represent a potential target for experimental structure determination aimed at obtaining a structural template for PrP(Sc) modeling.
Kuznetsov
Igor B
IB
Department of Biomathematical Sciences, Mount Sinai School of Medicine, Box 1023, One Gustave L. Levy Place, New York, NY 10029, USA. igor@ku.edu
Rackovsky
S
S
D000595:Amino Acid Sequence; D000818:Animals; D003587:Cytomegalovirus / Q000737:chemistry / Q000235:genetics*; D003627:Data Interpretation, Statistical; D008969:Molecular Sequence Data; D002679:Pan troglodytes / Q000821:virology; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics; D011328:Prions / Q000737:chemistry / Q000235:genetics*; D017385:Sequence Homology; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics*
D010446:Peptide Fragments; D011328:Prions; D014764:Viral Proteins