Effect of catechin EGCG in assembly of Hsp90 complex: co-chaperones

• Grant number: 14/15432-6
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: October 01, 2014
• End date: January 31, 2017
• Field of knowledge: Biological Sciences - Biochemistry - Chemistry of Macromolecules
• Principal Investigator: Lisandra Marques Gava Borges
• Grantee: Carolina Colleti
• Host Institution: Centro de Ciências Biológicas e da Saúde (CCBS). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil
• Associated research grant: 12/50161-8 - Study of the structure and function of the Hsp90 chaperone with emphasis on its role in cellular homeostasis, AP.TEM
• Associated scholarship(s): 16/01603-9 - Determining physical interactions required for R2TP complex assembly using biophysical and biochemical approaches, BE.EP.IC

Abstract

Proteins are the most versatile and complex biomolecules and have an active role in most biological processes, to achieve their function within the cell, proteins have to acquire their native form, ie, must be correctly folded. Molecular chaperones, also called heat shock proteins (Hsp) are capable to help other proteins in achieving their native form, these chaperones comprise several other functions in addition to it. Molecular chaperones can act promoting translocation of proteins into organelles; they operate as a quality control system of proteins that recognizes and deliver damaged proteins for degradation; may act in signal transduction as well as activate or inactivate signaling molecules. Hsp90 is a highly conserved and widely distributed molecular chaperone that has great importance, especially due to the high number of client or proteins or interactors (over 300); furthermore is involved in the mechanism of several diseases, eg, cancer and neurodegenerative diseases such as Parkinson's or Alzheimer's. Thus, the therapeutic potential of human Hsp90 is obvious, which makes it an excellent target for research, particularly with regard to their molecular mechanisms of interaction and inhibition. Following this research line, the scope of this project is to evaluate the interactions between human Hsp90 and co-chaperones Hop and Tom70; and especially the effects of the ligand/inhibitor EGCG (the key catechin of green tea) looking for knowledge on molecular mechanisms involved in this inhibition and its possible effects on the chaperone:co-chaperone complex assemblies. To achieve these goals spectroscopy and calorimetric techniques will be applied. (AU)