Characterization of PPARgamma-PGC-1alpha interaction mechanisms

• Grant number: 22/05028-0
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: November 01, 2022
• End date: October 31, 2023
• Field of knowledge: Biological Sciences - Biophysics - Molecular Biophysics
• Principal Investigator: Ana Carolina Migliorini Figueira
• Grantee: Marieli Mariano Gonçalves Dias
• Supervisor: Sebastian Thallmair
• Host Institution: Centro Nacional de Pesquisa em Energia e Materiais (CNPEM). Campinas , SP, Brazil
• Institution abroad: Frankfurt Institute for Advanced Studies (FIAS), Germany
• Associated to the scholarship: 19/10274-7 - Study of the PPARy-coregulators interactions and its relationship with adipogenesis and insulin resistance, BP.DR

Abstract

PPAR gamma is the main regulator of adipogenesis and insulin sensitization, and therefore it is widely studied as a therapeutic target for modulating the metabolic processes that involve obesity. PGC-1 alpha is a coregulator partner of PPARgamma, it acts together to regulate genes involved mainly in beta-oxidation and browning processes. Previous results from our group have shown that they can form non-canonical contacts and that this interaction can be affected by PPARgamma Ser273 phosphorylation, a process that occurs in an obesity state. This project proposes computational methodologies to elucidate the PPARgamma-PGC-1 alpha interaction interface. Modeling the tertiary structure of the protein complex is a tool extensively used for proteins with known crystallized structures. However, assembling complexes with intrinsically disordered partners, as PGC-1 alpha is a considerable challenging problem. The results obtained with this project will be of vital importance to provide relevant information about the PPARy mechanism of action, especially in the context of obesity. This could lead to the discovery of new targets unexplored for the development of drugs that addresses this receptor, with minimization of its known side effects. (AU)