title: Predicting proteasomal cleavage sites: a comparison of available methods.
abstract: The proteasome plays an essential role in the immune responses of vertebrates. By degrading intercellular proteins from self and non-self, the proteasome produces the majority of the peptides that are presented to cytotoxic T cells (CTL). There is accumulating evidence that the C-terminal, in particular, of CTL epitopes is cleaved precisely by the proteasome, whereas the N-terminal is produced with an extension, and later trimmed by peptidases in the cytoplasm and in the endoplasmic reticulum. Recently, three publicly available methods have been developed for prediction of the specificity of the proteasome. Here, we compare the performance of these methods on a large set of CTL epitopes. The best method, NetChop at www.cbs.dtu.dk/Services/NetChop, can capture approximately 70% of the C-termini correctly. This result suggests that the predictions can still be improved, particularly if more quantitative degradation data become available.
authors.affiliation: Center for Biological Sequence Analysis, BioCentrum-DTU, Technical University of Denmark, Lyngby, Denmark.
authors.forename: Patricia
authors.initials: P
authors.lastname: Saxová
authors.forename: Søren
authors.initials: S
authors.lastname: Buus
authors.forename: Søren
authors.initials: S
authors.lastname: Brunak
authors.forename: Can
authors.initials: C
authors.lastname: Keşmir
mesh_terms: D000465:Algorithms; D000595:Amino Acid Sequence; D019295:Computational Biology / Q000379:methods; D003198:Computer Simulation; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D030562:Databases, Protein; D000939:Epitopes / Q000737:chemistry*; D015234:HLA-A Antigens / Q000737:chemistry; D015235:HLA-B Antigens / Q000737:chemistry; D006801:Humans; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry; D046988:Proteasome Endopeptidase Complex; D011506:Proteins / Q000737:chemistry / Q000378:metabolism; D020539:Sequence Analysis, Protein / Q000379:methods*
chemical_list: D000939:Epitopes; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D009097:Multienzyme Complexes; D010455:Peptides; D011506:Proteins; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex