title: Phylogenetic and primary sequence characterization of cathepsin B cysteine proteases from the oxymonad flagellate Monocercomonoides.
abstract: Cysteine proteases are crucial for general lysosomal function and for the pathogenic mechanisms of many protistan parasites. Cathepsin B cysteine proteases are currently defined by the presence of the "occluding loop" motif and have been best characterized from humans and their parasites. Though related to a variety of pathogenic excavate flagellates, oxymonads are themselves commensals. While studying this cell biologically aberrant protist lineage, we identified 11 different cathepsin B homologues. These were found to be expressed, at comparable levels to common house-keeping genes, such as elongation factor 1-alpha, alpha-tubulin, beta-tubulin, and glyceraldehyde phosphate dehydrogenase. Primary structure examination of the cathepsin B homologues identified putative signal peptide sequences, and the pre-, pro-, and mature domains of the protein. However, the occluding loop motif was either partially or entirely absent. Comparative genomics, sequence alignment, and phylogenetics of cathepsin sequences from across the diversity of eukaryotes demonstrated that absence of the occluding loop is not a feature exclusive to oxymonads, but is relatively common, suggesting that the "occluding loop" should no longer be used as the defining feature of the cathepsin B subfamily. Overall, this report identifies an abundant protein family in oxymonads, and provides insight both into the evolution and classification of cathepsin B cysteine proteases.
authors.affiliation: Department of Biological Sciences, University of Calgary, 2500 University Drive NW, Calgary, Alberta, Canada T2N 1N4. jbd26@cam.ac.uk
authors.forename: Joel B
authors.initials: JB
authors.lastname: Dacks
authors.forename: Teklu
authors.initials: T
authors.lastname: Kuru
authors.forename: Natalia A
authors.initials: NA
authors.lastname: Liapounova
authors.forename: Lashitew
authors.initials: L
authors.lastname: Gedamu
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D002401:Cathepsin B / Q000737:chemistry* / Q000235:genetics* / Q000302:isolation & purification; D017124:Conserved Sequence; D056890:Eukaryota / Q000145:classification / Q000201:enzymology* / Q000235:genetics*; D005057:Eukaryotic Cells / Q000201:enzymology; D015870:Gene Expression; D006801:Humans; D008969:Molecular Sequence Data; D010802:Phylogeny; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA
chemical_list: D002401:Cathepsin B