Nuclear receptor boxes

The crystal structures of 104a and 104b bound to a complex consisting of the RARyS ligand binding domain with the second nuclear receptor box peptide of the SRC-1 coactivator show different contacts with helix Hll... 

Cyclization of peptides is an established strategy to stabilize short peptides in an a-helical conformation. Concomitantly, different types of cyclic peptides have been explored as inhibitors of the nuclear receptor-coactivator interaction. Guy et al. have created a library of a-helical constrained peptidomimetics, based on the second nuclear receptor box found in the SRC2 coactivator, by the introduction of a macrolactam bridge [56-58]. The macrolactam bridge induces an a-helical... 

Gustafsson, J.A., Hubbard, R.E., Brzozowski, A.M. and Pike, A.C. (2002) Interaction of transcriptional intermediary factor 2 nuclear receptor box peptides with the coactivator binding site of estrogen receptor a. The Journal of Biological Chemistry, 277, 21862—21868. 

Nuclear receptors exert their different transcriptional functions through interactions with and the recruitment of co-factors to responsive promoters. Co-factors are either positive or negative regulatory proteins and are classified as co-activators, which promote, or co-repressors, which attenuate the activity of nuclear hormone receptors [46]. The molecular mechanisms that regulate the mutually exclusive interactions of the nuclear receptor with either class of co-factors have been analysed by crystallographic studies. Functional and structural studies have shown that co-activators interact with the transactivation function (AF) of nuclear hormone receptors via short, leucine-rich motifs (LXXLL) termed NR boxes , thereby transducing hormonal signals to the basal transcription machinery [47]. 

To sum up determinants that control the developmental programme of Drosophila are highly conserved nuclear receptors. They have similar DBDs with a DNA-recognition helix. The DNA recognition site, the P-box, has a typical Zn2+(Cys)4 motif (these motifs do not bind direcdy to DNA, but help to direct the recognition helix to the major groove of the DNA). 

PNRC Two proline-rich nuclear receptor coregulatory proteins (PNRC1 and PNRC2) were cloned from a mammary gland cDNA library (97,98). These proteins are relatively small, with molecular weights of 16 kDa and 35 kDa, respectively. Both PNRCs interacted with hormone receptors in a ligand-dependent manner, mediated by an activation function domain that contains an NR box-like... 

MAT locus (in yeast) 471 mediator 471 nuclear receptors 464 promoter 449 promoter-proximal elements 455 repression domain 462 repressors 449 RNA polymerase II 450 silencer sequences 472 TATA box 454 upstream activating sequences (UASs) 457 yeast two-hybrid system 480 zinc finger 463... 

Similar to how the coactivators use the LXXLL motif as a docking point, the corepressors contain an LXXIIXXXL peptide referred to as the corepressor nuclear receptor (CoRNR) box [66]. The precise nature of the interaction between corepressors and NRs remained elusive before the solution of the crystal structure between PPARa and a peptide from SMRT. As mentioned briefly in a previous section, this structure shows that the CoRNR box occupies the same general site on PPARa as the coactivator LXXLL motif. However,... 

Two important cis-acting elements in the ALDH2 promoter have been studied. A site located from 79 to 116 bp upstream of the ATG initiating translation is bound by nuclear factor(s) present in all cells tested the CCAAT box in this region is important for transcriptional activity, and appears to be bound primarily by the transcription factor NF-Y/CP1 [46]. There is a site, approximately 300 bp upstream of the ATG, at which HNF-4 and retinoid X receptors can bind, as can the apolipoproteins regulatory protein (ARP-1) [47, 48]. Transcription from this promoter can be activated by HNF-4 and RXRs [47, 48]. 

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