D
IPR003902

Transcription regulator GCM domain

InterPro entry
Short nameTscrpt_reg_GCM
Overlapping
homologous
superfamilies
 
GCM, small domain (IPR043021)

Description

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 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'
[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 is 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 β-sheets, respectively, with three small helical segments packed against the same side of the two β-sheets. The GCM domain exercises a novel mode of sequence-specific DNA recognition, where the five-stranded β-pleated sheet inserts into the major groove of the DNA. Residues protruding from the edge strand of the β-pleated sheet and the following loop and strand contact the bases and backbone of both DNA strands, providing specificity for its DNA target site.

References

1.The gcm-motif: a novel DNA-binding motif conserved in Drosophila and mammals. Akiyama Y, Hosoya T, Poole AM, Hotta Y. Proc. Natl. Acad. Sci. U.S.A. 93, 14912-6, (1996). View articlePMID: 8962155

2.The regulator of early gliogenesis glial cells missing is a transcription factor with a novel type of DNA-binding domain. Schreiber J, Sock E, Wegner M. Proc. Natl. Acad. Sci. U.S.A. 94, 4739-44, (1997). View articlePMID: 9114061

3.Structural requirements for DNA binding of GCM proteins. Schreiber J, Enderich J, Wegner M. Nucleic Acids Res. 26, 2337-43, (1998). View articlePMID: 9580683

4.Protein stability and domain topology determine the transcriptional activity of the mammalian glial cells missing homolog, GCMb. Tuerk EE, Schreiber J, Wegner M. J. Biol. Chem. 275, 4774-82, (2000). View articlePMID: 10671510

5.Structure of the GCM domain-DNA complex: a DNA-binding domain with a novel fold and mode of target site recognition. Cohen SX, Moulin M, Hashemolhosseini S, Kilian K, Wegner M, Muller CW. EMBO J. 22, 1835-45, (2003). View articlePMID: 12682016

GO terms

molecular function

cellular component

  • None

Cross References

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