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Orphan nuclear receptor NGFI‐B forms dimers with nonclassical interface
Author(s) -
Calgaro Marcos R.,
Neto Mario de Oliveira,
Figueira Ana Carolina M.,
Santos Maria A.M.,
Portugal Rodrigo V.,
Guzzi Carolina A.,
Saidemberg Daniel M.,
Bleicher Lucas,
Vernal Javier,
Fernandez Pablo,
Terenzi Hernán,
Palma Mario Sergio,
Polikarpov Igor
Publication year - 2007
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1110/ps.062692207
Subject(s) - chemistry , nuclear receptor , nuclear receptor coactivator 1 , dimer , retinoid x receptor , nuclear receptor coactivator 2 , pregnane x receptor , nuclear receptor co repressor 1 , receptor , nuclear localization sequence , stereochemistry , crystallography , biophysics , transcription factor , biochemistry , biology , organic chemistry , gene , cytoplasm
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.