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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.)

Orphan nuclear receptor NGFI-B forms dimers with nonclassical interface

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Autor(es):
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Calgaro, Marcos R. ; Oliveira Neto, Mario de ; Figueira, Ana Carolina M. ; Santos, Maria A. M. ; Portugal, Rodrigo V. ; Guzzi, Carolina A. ; Saidemberg, Daniel M. ; Bleicher, Lucas ; Vernal, Javier ; Fernandez, Pablo ; et al
Número total de Autores: 11
Tipo de documento: Artigo Científico
Fonte: Protein Science; v. 16, n. 8, p. 1762-1772, Aug. 2007.
Área do conhecimento: Ciências Biológicas - Biofísica
Assunto(s):Biofísica   Fatores de crescimento neural   Glucocorticoides
Resumo

The orphan receptor nerve growth factor-induced B (NGFI-B) is a member of the nuclear receptor's subfamily 4A (Nr4a). NGFI-B was shown to be capable of binding both as a monomer to an extended half-site containing a single AAAGGTCA motif and also as a homodimer to a widely separated everted repeat, as opposed to a large number of nuclear receptors that recognize and bind specific DNA sequences predominantly as homo- and/or heterodimers. To unveil the structural organization of NGFI-B in solution, we determined the quaternary structure of the NGFI-B LBD by a combination of ab initio procedures from small-angle X-ray scattering (SAXS) data and hydrogen-deuterium exchange followed by mass spectrometry. Here we report that the protein forms dimers in solution with a radius of gyration of 2.9 nm and maximum dimension of 9.0 nm. We also show that the NGFI-B LBD dimer is V-shaped, with the opening angle significantly larger than that of classical dimer's exemplified by estrogen receptor (ER) or retinoid X receptor (RXR). Surprisingly, NGFI-B dimers formation does not occur via the classical nuclear receptor dimerization interface exemplified by ER and RXR, but instead, involves an extended surface area composed of the loop between helices 3 and 4 and C-terminal fraction of the helix 3. Remarkably, the NGFI-B dimer interface is similar to the dimerization interface earlier revealed for glucocorticoid nuclear receptor (GR), which might be relevant to the recognition of cognate DNA response elements by NGFI-B and to antagonism of NGFI-B-dependent transcription exercised by GR in cells. (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: 02/05329-6 - Expressão, purificação e estudos estruturais do receptor X do pregnano (PXR)
Beneficiário:Marcos Román Calgaro
Linha de fomento: Bolsas no Brasil - Doutorado