GCM transcription factors
structure of the gcm domain bound to dna
In molecular biology, the 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 homologues. In GCM transcription factors the N-terminal moiety contains a DNA-binding domain of 150 amino acids. 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'. The GCM motif contains many conserved basic amino acid residues, seven cysteine residues, and four histidine residues. 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. The GCM domain as a new class of Zn-containing DNA-binding domain with no similarity to any other DNA-binding domain. 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.
- Akiyama Y, Hosoya T, Poole AM, Hotta Y (December 1996). "The gcm-motif: a novel DNA-binding motif conserved in Drosophila and mammals". Proc. Natl. Acad. Sci. U.S.A. 93 (25): 14912–6. PMC . PMID 8962155. doi:10.1073/pnas.93.25.14912.
- Schreiber J, Sock E, Wegner M (April 1997). "The regulator of early gliogenesis glial cells missing is a transcription factor with a novel type of DNA-binding domain". Proc. Natl. Acad. Sci. U.S.A. 94 (9): 4739–44. PMC . PMID 9114061. doi:10.1073/pnas.94.9.4739.
- Schreiber J, Enderich J, Wegner M (May 1998). "Structural requirements for DNA binding of GCM proteins". Nucleic Acids Res. 26 (10): 2337–43. PMC . PMID 9580683. doi:10.1093/nar/26.10.2337.
- Tuerk EE, Schreiber J, Wegner M (February 2000). "Protein stability and domain topology determine the transcriptional activity of the mammalian glial cells missing homolog, GCMb". J. Biol. Chem. 275 (7): 4774–82. PMID 10671510. doi:10.1074/jbc.275.7.4774.
- Cohen SX, Moulin M, Hashemolhosseini S, Kilian K, Wegner M, Muller CW (April 2003). "Structure of the GCM domain-DNA complex: a DNA-binding domain with a novel fold and mode of target site recognition". EMBO J. 22 (8): 1835–45. PMC . PMID 12682016. doi:10.1093/emboj/cdg182.