Structural Prediction of NGFI-B and Nor1 Ligand Binding Domains

PABLO M. FERNÁNDEZ; GABRIEL A VALDIVIESO; CARLOS F. AGUILAR

Congreso; XXXVII Annual Meeting of the Argentine Society for Biochemistry and Molecular Biology Research; 2001

The orphan nuclear receptors NGFI-B and Nor1 have been implicated in the regulation of hypothalamic and pituitary functions as well as the adrenocortical steroidogenesis. Both proteins are expressed in the pituitary gland and adrenal cortex, and ACTH and Angiotensin II (AngII) treatment of adrenal fasciculata cells induces its expression. These proteins activated the expression of genes encoding steroidogenic enzymes as P450c21, acting as intermediates in the long term consequences of ACTH or AngII treatment. The overall structural and functional organization of NGFI-B/Nur77 and Nor1 is similar, but Nor1 is not an efficient substitute for the NGFI-B/Nur77 activation of the POMC gene expression in pituitary glands. As the activation occurs when NGFI-B acts as homo or heterodimers, in order to better understand this difference we used computing analysis to develop models for the ligand binding domains of NGFI-B and Nor1, according to crystallographic analysis of known sequences. The analysis showed that important residues contributing to the homo and heterodimeryzation of these nuclear receptors are conserved in NGFI-B but not in Nor1 sequence. These changes may determine important differences in the spatial distribution of the different domains, making difficult the homo and heterodimeryzation process in Nor1 and explaining the differences observed.