Food and water were provided ad libitum throughout the experiments

three scaffold proteins and comprise representative members of aaRSs from both classes. This, as far as we know, is also the first report of a YRS enzyme being found in a MARS complex. One theory for the role of the MARS complex, put forward to explain the presence of ERS and not QRS in the yeast complex, is to recruit additional tRNA-binding domains to aaRSs that lack them. The presence of MRS, which also contains a myftRNA binding domain, in the Toxoplasma MARS MedChemExpress Digitoxin complex is therefore puzzling if this is also the driver for inclusion in the Toxoplasma complex. The choice of aaRSs and the exact function of the MARS complex in Toxoplasma therefore remains a mystery especially in light of our genetic analyses in both virulent 8 Toxoplasma Multi-Aminoacyl-tRNA Synthetase Complex and non-virulent but cystogenic, T. gondii strains showing that Tg-p43 is not essential for viability or pathogenesis of the parasite. Together with what is known about the non-essential nature of AIMPs in yeast ] and humans, our results further suggest that the contribution of the MARS complex to posttranscriptional gene control must be subtle. Assembly of the complex Based on PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19630074 the similarity of the overall domain structures and the degree of homology between the Tg-p43 and the yeast Arc1p proteins it was assumed that assembly of the Toxoplasma complex would be driven by similar mechanisms. The associations between the yeast Arc1p protein and its ERS and MRS partners have been attributed to pairwise dimerizations occurring at distinct interfaces in the GST domain of the scaffold protein. The presence of MRS, QRS, and ERS, all of which possess GST-like motifs, in the Toxoplasma complex was therefore not surprising but the inclusion of YRS was unexpected as its N-terminal extension is predicted to be highly disordered. Until more structural information is available for the N-terminal region of the Toxoplasma YRS protein, it remains to be seen in the GST motif is structurally conserved despite this apparent sequence divergence. We were able to reveal a direct association of MRS and YRS with the Tg-p43 and we subsequently showed that only the Nterminal region of this scaffold protein, harbouring the GST-motif, was necessary for the association. Although it was not possible to demonstrate direct interactions for the QRS and ERS proteins, because modifications to these genes compromised the viability of the parasite, we did show that the presence of QRS in the highmolecular weight fraction depended on Tg-p43. We cannot however exclude the possibility that QRS is recruited to the MARS complex through an interaction with ERS. Dissecting the interactions of these essential proteins will require biophysical characterisation of pairwise interactions in native MARS complex subassemblies or recombinant proteins. Heterogeneity in MARS composition and sizes Toxoplasma Multi-Aminoacyl-tRNA Synthetase Complex left. On the right, three different class averages generated by re-aligning only the central regions of the 137 views on the left are presented. The efficacy of many PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19632179 novel targeted cancer therapies can be predicted by the detection of specific biomarkers in the tumor. The FDA has indicated that if the identification of a specific biomarker is required for the safe and efficacious administration of a drug, a well-validated FDA approved companion diagnostic assay is required for that drug. The optimal approval path for a new targeted therapy and its companion diagnostic is a para