GCM transcription factors

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PDB 1odh EBI.jpg
structure of the gcm domain bound to dna
Symbol GCM
Pfam PF03615
Pfam clan CL0274
InterPro IPR003902
SCOP 1odh

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.[1][2][3][4] 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'.[1][2][3] The GCM motif contains many conserved basic amino acid residues, seven cysteine residues, and four histidine residues.[1] 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.[3] The GCM domain as a new class of Zn-containing DNA-binding domain with no similarity to any other DNA-binding domain.[5] 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.


  1. ^ a b c 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 26236Freely accessible. PMID 8962155. doi:10.1073/pnas.93.25.14912. 
  2. ^ a b 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 20794Freely accessible. PMID 9114061. doi:10.1073/pnas.94.9.4739. 
  3. ^ a b c Schreiber J, Enderich J, Wegner M (May 1998). "Structural requirements for DNA binding of GCM proteins". Nucleic Acids Res. 26 (10): 2337–43. PMC 147556Freely accessible. PMID 9580683. doi:10.1093/nar/26.10.2337. 
  4. ^ 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. 
  5. ^ 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 154474Freely accessible. PMID 12682016. doi:10.1093/emboj/cdg182. 

This article incorporates text from the public domain Pfam and InterPro IPR003902