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Complex between thyroid hormone receptor and coactivator: formation and characterization.

Grant number: 13/26507-4
Support type:Scholarships in Brazil - Master
Effective date (Start): April 01, 2014
Effective date (End): February 29, 2016
Field of knowledge:Biological Sciences - Biophysics - Molecular Biophysics
Principal Investigator:Ana Carolina Migliorini Figueira
Grantee:Tábata Renée Doratioto
Home Institution: Centro Nacional de Pesquisa em Energia e Materiais (CNPEM). Ministério da Ciência, Tecnologia, Inovações e Comunicações (Brasil). Campinas , SP, Brazil

Abstract

A significative part of world population suffers whit thyroid related problems. Thyroid hormone regulates a lot of functions from endocrine system by its interaction with thyroid hormone receptor (TR). Thyroid hormone presence induces a conformational exchange in its receptor, TR, which leads to the interaction with a coactivator protein like GRIP, for example. TR (association) with coactivator helps in chromatin opening through histone acetylases leading to transcription activation of several genes, mainly of genes related to proteins wich regulate basal metabolism.This project aims to study nuclear receptor-coactivators complex formation and characterization to map its interfaces of interaction. To reach this objective it will be executed assays to evaluate complex stoichiometry, binding affinity among these proteins and also the ligand role in these receptors.Proteins will be purified and complexes will be formed by pull down like assays or coexpression. Complex will be analysed by mass spechometry using cross-linking reaction to map the interaction among NR-CoA, looking for to identify new interactions. Complex stoichiometry will be investigated through analytical ultracentrifugation; the binding affinity among the proteins will be executed applying fluorescence anisotropy. Finally, it will be executed crystallization assays of complex of complex which will bring a better understanding about their structures. It's important to mention that knowing the interactions among these proteins will give subsidy for better compreention about TR action mechanism. This is direct related to drug design once the surface of interaction between two proteins could be considered as a new target for ligands activation.

Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
RIBEIRO FILHO, HELDER VERAS; VIDEIRA, NATALIA BERNARDI; BRIDI, ALINE VILLANOVA; TITTANEGRO, THAIS HELENA; HELENA BATISTA, FERNANDA APARECIDA; DE CARVALHO PEREIRA, JOSE GERALDO; LOPES DE OLIVEIRA, PAULO SERGIO; BAJGELMAN, MARCIO CHAIM; LE MAIRE, ALBANE; MIGLIORINI FIGUEIRA, ANA CAROLINA. Screening for PPAR Non-Agonist Ligands Followed by Characterization of a Hit, AM-879, with Additional No-Adipogenic and cdk5-Mediated Phosphorylation Inhibition Properties. FRONTIERS IN ENDOCRINOLOGY, v. 9, FEB 1 2018. Web of Science Citations: 2.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.