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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Ligand induced interaction of thyroid hormone receptor beta with its coregulators

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Autor(es):
Valadares, Napoleau F. [1] ; Polikarpov, Igor [1] ; Garratt, Richard C. [1]
Número total de Autores: 3
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Inst Fis Sao Carlos, Dept Fis & Informat, BR-13560970 Sao Carlos, SP - Brazil
Número total de Afiliações: 1
Tipo de documento: Artigo Científico
Fonte: JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY; v. 112, n. 4-5, p. 205-212, DEC 2008.
Citações Web of Science: 15
Resumo

Thyroid hormones exert most of their physiological effects through two thyroid hormone receptor (TR) subtypes, TR alpha and TR beta, which associate with many transcriptional coregulators to mediate activation or repression of target genes. The search for selective TR beta ligands has been stimulated by the finding that several pharmacological actions mediated by TR beta might be beneficial in medical conditions such as obesity, hypercholesterolemia and diabetes. Here, we present a new methodology which employs surface plasmon resonance to investigate the interactions between TR beta ligand binding domain (LBD) complexes and peptides derived from the nuclear receptor interaction motifs of two of its coregulators, SRC2 and DAX1. The effect of several TR beta ligands, including the TR beta selective agonist GC-I and the TR beta selective antagonist NH-3, were investigated. We also determined the kinetic rate constants for the interaction of TR beta-T3 with both coregulators, and accessed the thermodynamic parameters for the interaction with DAX1. Our findings Suggest that flexibility plays an important role in the interaction between the receptor and its coregulators. and point out important aspects of experimental design that should be addressed when using TR beta LBD and its agonists. Furthermore, the methodology described here may be useful for the identification of new TR beta ligands. (C) 2008 Elsevier Ltd. All rights reserved. (AU)

Processo FAPESP: 02/14205-9 - Estudos computacionais baseados em estrutura dos receptores de hormônios tiroidianos e determinação de sua atividade em células humanas
Beneficiário:Napoleão Fonseca Valadares
Linha de fomento: Bolsas no Brasil - Doutorado Direto