| Abstract | GCM transcription factors are a family of proteins which contain a GCM motif. The GCM motif is a domain that has been
identified in proteins belonging to a family of
transcriptional regulators involved in fundamental developmental processes which comprise Drosophila melanogaster GCM and its mammalian
homologs [ 8962155, 9114061, 9580683, 10671510]. IN GCM transcription factors the N-terminal moiety contains a DNA-binding domain of 150 residues. Sequence conservation is
highest in this GCM domain. In contrast, the C-terminal moiety contains one or two transactivating regions and is only poorly conserved. The GCM motif has been shown to be a DNA binding domain that recognises preferentially the nonpalindromic octamer 5'-ATGCGGGT-3' [8962155, 9114061, 9580683]. The GCM motif contains many conserved basic amino acid residues, seven cysteine residues, and four histidine residues [8962155]. The conserved cysteines are involved in shaping the overall conformation of the domain, in the process of DNA binding and in the redox regulation of DNA binding [9580683]. The
GCM domain as a new class of Zn-containing DNA-binding domain with no similarity to any other DNA-binding domain [12682016]. The GCM domain consists of a large and
a small domain tethered together by one of the two Zn ions present in the structure. The large and the small domains comprise five- and three-stranded
beta-sheets, respectively, with three small helical segments packed against the same side of the two beta-sheets. The GCM domain exercises a novel mode of
sequence-specific DNA recognition, where the five-stranded beta-pleated sheet inserts into the major groove of the DNA. Residues protruding from the edge strand of
the beta-pleated sheet and the following loop and strand contact the bases and backbone of both DNA strands, providing specificity for its DNA target site. |
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