| Full text | |
| Author(s): Show less - |
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
Total Authors: 11
|
| Document type: | Journal article |
| Source: | Protein Science; v. 16, n. 8, p. 1762-1772, Aug. 2007. |
| Field of knowledge: | Biological Sciences - Biophysics |
| Abstract | |
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) | |