The DNA binding domains (DBDs) of members of the NR family are, in general, highly conserved, displaying approximately 60% identity at the amino acid level across the en-
Chicken ovalbumin upstream promoter-transcription factors (COUP-TFI,II, III) Hepatic nuclear factor-4 (HNF-4) NGFI-B and related proteins
Ligand-dependent transcriptional activation function core (AF2) Nuclear localization signal Ligand-independent transcriptional activation function (AF1) Silencing function
tire family. The DBD of both RARs and RXRs, and of all NRs, is composed of approximately 66-80 amino acids that are organized into two C2C2 zinc finger motifs (see Figs. 7.16 and 7.17), each of which tetrahedrally coordinates one zinc ion (134, 136). These two zinc fingers fold into a single structural motif comprised of two a helices, the recognition and support helices that are located on the knuckle on the carboxyl side of each zinc finger (134, 136). The two a-helices play very different roles in the function of the receptors: the recognition helii sits in the major groove of DNA and makes specific contacts with discriminating nucleotides within the response element; the support helix is oriented perpendicularly to the recognition helix and does not contact DNA at all (134,136). Rather, the support helii makes specific protein-protein contacts with and effectively buttresses the recognition helix into the major groove. This concept is illustrated schematically in Fig. 7.21. Biochemical (137,138) and crystallographic (134, 136) studies have revealed that three amino acids within the recognition helix are crucial for response element discrimination by most NRs.
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Complete Guide to Preventing Skin Cancer. We all know enough to fear the name, just as we do the words tumor and malignant. But apart from that, most of us know very little at all about cancer, especially skin cancer in itself. If I were to ask you to tell me about skin cancer right now, what would you say? Apart from the fact that its a cancer on the skin, that is.