Orphan nuclear receptor NGFI-B forms dimers with nonclassical interface
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Data
2007-08-01
Autores
Calgaro, Marcos R.
Neto, Mario de Oliveira
Figueira, Ana Carolina M.
Santos, Maria A.M.
Portugal, Rodrigo V.
Guzzi, Carolina A.
Saidemberg, Daniel M. [UNESP]
Bleicher, Lucas
Vernal, Javier
Fernandez, Pablo
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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. Published by Cold Spring Harbor Laboratory Press. Copyright © 2007 The Protein Society.
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Palavras-chave
Glucocorticoid nuclear receptor, Hydrogen-deuterium exchange, NGFI-B, Orphan nuclear receptor, SAXS, cell nucleus receptor, dimer, estrogen receptor, helix loop helix protein, nuclear receptor Nur77, retinoid X receptor, amino acid sequence, animal cell, controlled study, dimerization, fluorescence spectroscopy, mass spectrometry, nonhuman, priority journal, protein binding, protein conformation, protein folding, protein interaction, protein secondary structure, protein stability, protein structure, receptor binding, X ray crystallography, Circular Dichroism, Dimerization, DNA-Binding Proteins, Mass Spectrometry, Models, Biological, Models, Molecular, Protein Structure, Secondary, Receptors, Cytoplasmic and Nuclear, Receptors, Glucocorticoid, Receptors, Steroid, Scattering, Small Angle, Solutions, Transcription Factors
Como citar
Protein Science, v. 16, n. 8, p. 1762-1772, 2007.