Figure 6 Secretomes of T. brucei gambiense and CT99021 mouse L. donovanii share functional homology. Functional categories from T. brucei gambiense and L. donovanii secretomes were compared (A). Proteins from T. brucei total proteome and glycosome were also classified into functional categories (B). On the x-axis, the categories are the following: 1. unassigned function, 2. folding and degradation, 3. nucleotide metabolism, 4. carbohydrate metabolism, 5. amino acid metabolism, 6. protein synthesis, 7. signaling, 8. cell cycle and organization, 9. lipid and cofactor, 10. transport, 11.

redox, and 12. RNA/DNA metabolism. The y-axis shows the percentage of each category for each proteome/secretome. In summary, comparison of both the protein accessions and the functional categories similarly demonstrated features specific to the different www.selleckchem.com/products/FK-506-(Tacrolimus).html compartments, and a close relationship between the secretome of Trypanosoma and Leishmania. How are Trypanosoma proteins secreted? 1- Secreted proteins do not contain a transit peptide If trypanosomes use

the classical secretion pathway, most secreted proteins should carry an N-terminal extension (transit peptide). SignalP is currently the most popular software for predicting the presence of a N-terminal transit peptide and the associated cleavage site [21]. We performed a genome-wide screen of the Trypanosoma proteome using SignalP and identified 1445 proteins as predicted to contain a transit peptide (see additional file 6, Table S6), 61% without any known function. Of the remaining 561 proteins, many were known to be secreted or located at the plasma membrane, including 128 VSGs, 16 invariant surface proteins (ISG), 15 procyclin surface proteins, 14 bloodstream stage alanine-rich surface proteins (BARPs), 36 receptors for adenylate cyclase (GRESAGs), 28 transporters, 13 cysteine peptidases/clan CA/family

C1 and family C2, seven transialidases, and many enzymes involved in lipid modification, glycosylation, and GPI (Glycosylphosphatidylinositol) anchoring. To focus specifically on the secreted proteins, i.e., proteins with no transmembrane span, we further assessed the occurrence of such domains using the transmembrane predictor TMHMM (transmembrane protein topology with a Hidden Markov Model) [22]. 660 proteins Aurora Kinase were simultaneously predicted to contain a transit peptide by SignalP and not to contain transmembrane domains by TMHMM. Quite unexpectedly, only 30 out of the 444 secretome proteins experimentally identified in this work belonged to the predicted secretome. Although not secreted by the classical secretory pathway, proteins devoid of an N-terminal signal peptide may still be secreted. We used the SecretomeP software [23] to predict such proteins in the Trypanosoma genome (additional file 6, Table S6). Depending on the selected threshold score, different proportions of known proteins and proteins having unassigned functions were computed. A score between 0.8 and 0.