| Grant number: | 14/06829-0 |
| Support type: | Scholarships abroad - Research Internship - Doctorate |
| Effective date (Start): | June 01, 2014 |
| Effective date (End): | October 31, 2014 |
| Field of knowledge: | Biological Sciences - Biochemistry - Chemistry of Macromolecules |
| Principal Investigator: | Julio Cesar Borges |
| Grantee: | Thiago Vargas Seraphim |
| Supervisor abroad: | Walid A. Houry |
| Home Institution: | Instituto de Química de São Carlos (IQSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil |
| Local de pesquisa : | University of Toronto (U of T), Canada |
| Associated to the scholarship: | 10/19242-6 - Study of the functional cycle of the Hsp90 molecular chaperone of protozoa and of the action of the co-chaperone Activator of the Hsp90 ATPase Activity - AHA1, BP.DR |
Abstract Molecular chaperones are proteins involved in protein quality control and homeostasis in the cell. Among several molecular chaperone families, the Hsp90 is essential for cell growth, including cellular adaptation, differentiation and virulence in protozoa, such as those of the genus Leishmania and Plasmodium. The functional cycle of the Hsp90 is tightly regulated by nucleotides and cochaperones, one of them is Aha1. Aha1 is formed by two domains and stimulates the low Hsp90 ATPase activity by several folds. Although the Hsp90 stimulation occurs by the full length Aha1, the exact role of each Aha1 domain remains controversial. Also, understanding peculiarities of the Hsp90-Aha1 complex of protozoa is an opportunity to make feasible the development of new therapeutics since Hsp90 is a good target for inhibition and Aha1 is involved in Hsp90 desensitization to inhibitors. We structurally characterized the full length Leishmania braziliensis and Plasmodium falciparum Aha1 (LbAha1 and PfAha1, respectively) and together with bioinformatics analysis, it was suggested that both proteins are organized structurally different. Thus, in this project we propose investigate the functional consequence of the divergent structural organization between LbAha1 and PfAha1, and the role of each domain by yeast complementation assays. Also, the role that Aha1 plays in thermotolerance and Hsp90 desensitization against inhibition are targets of our study. (AU) | |