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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.)

Probing conformational changes in orphan nuclear receptor: The NGFI-B intermediate is a partially unfolded dimer

Texto completo
Autor(es):
Garcia, Wanius [1] ; Figueira, Ana Carolina M. [1] ; Neto, Mario de Oliveira [1] ; de Guzzi, Carolina A. [1] ; Buzza, Hilde H. [1] ; Portugal, Rodrigo V. [1] ; Calgaro, Marcos R. [1] ; Polikarpov, Igor [1]
Número total de Autores: 8
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Inst Fis Sao Carlos, BR-13560970 Sao Carlos, SP - Brazil
Número total de Afiliações: 1
Tipo de documento: Artigo Científico
Fonte: Biophysical Chemistry; v. 137, n. 2-3, p. 81-87, OCT 2008.
Citações Web of Science: 1
Resumo

Human nerve growth factor-induced B (NGFI-B) is a member of the NR4A subfamily of orphan nuclear receptors (NRs). Lacking identified ligands, orphan NRs show particular co-regulator proteins binding properties, different from other NRs, and they might have a non-classical quaternary organization. A body of evidence suggests that NRs recognition of and binding to ligands, DNA, homo- and heterodimerization partners and co-regulator proteins involve significant conformational changes of the NR ligand-binding domains (LBDs). To shed light on largely unknown biophysical properties of NGFI-B, here we studied structural organization and unfolding properties of NGFI-B ligand (like)-binding domain induced by chemical perturbation. Our results show that NGFI-B LBD undergoes a two-state guanidine hydrochloride (GndHCl) induced denaturation, as judged by changes in the a-helical content of the protein monitored by circular dichroism spectroscopy (CD). In contrast, changes in the tertiary structure of NGFI-B LBD, reported by intrinsic fluorescence, reveal a clear intermediate state. Additionally, SAXS results demonstrate that the intermediate observed by intrinsic fluorescence is a partially folded homodimeric structure, which further unfolds without dissociation at higher GndHCl concentrations. This partially unfolded dimeric assembly of NGFI-B LBD might resemble an intermediate that this domain access momentarily in the native state upon interactions with functional partners. (C) 2008 Elsevier B.V. All rights reserved. (AU)

Processo FAPESP: 02/14041-6 - Estudos estruturais das interações dos receptores dos hormônios tireoideanos com os seus elementos responsivos do DNA
Beneficiário:Mario de Oliveira Neto
Linha de fomento: Bolsas no Brasil - Doutorado Direto
Processo FAPESP: 06/00182-8 - Biofísica estrutural dos receptores nucleares e proteínas relacionadas
Beneficiário:Igor Polikarpov
Linha de fomento: Auxílio à Pesquisa - Temático
Processo FAPESP: 03/09462-5 - Estudos estruturais e funcionais dos receptores nucleares dos hormônios tireoideanos: em busca de novos ligantes
Beneficiário:Ana Carolina Migliorini Figueira
Linha de fomento: Bolsas no Brasil - Doutorado Direto