Multidomain organization of eukaryotic guanine nucleotide exchange translation initiation factor eIF-2B subunits revealed by analysis of conserved sequence motifs

Protein Sci. 1995 Aug;4(8):1608-17. doi: 10.1002/pro.5560040819.


Computer-assisted analysis of amino acid sequences using methods for database screening with individual sequences and with multiple alignment blocks reveals a complex multidomain organization of yeast proteins GCD6 and GCD1, and mammalian homolog of GCD6-subunits of the eukaryotic translation initiation factor eIF-2B involved in GDP/GTP exchange on eIF-2. It is shown that these proteins contain a putative nucleotide-binding domain related to a variety of nucleotidyltransferases, most of which are involved in nucleoside diphosphate-sugar formation in bacteria. Three conserved motifs, one of which appears to be a variant of the phosphate-binding site (P-loop) and another that may be considered a specific version of the Mg(2+)-binding site of NTP-utilizing enzymes, were identified in the nucleotidyltransferase-related domain. Together with the third unique motif adjacent to the the P-loop, these motifs comprise the signature of a new superfamily of nucleotide-binding domains. A domain consisting of hexapeptide amino acid repeats with a periodic distribution of bulky hydrophobic residues (isoleucine patch), which previously have been identified in bacterial acetyltransferases, is located toward the C-terminus from the nucleotidyltransferase-related domain. Finally, at the very C-termini of GCD6, eIF-2B epsilon, and two other eukaryotic translation initiation factors, eIF-4 gamma and eIF-5, there is a previously undetected, conserved domain. It is hypothesized that the nucleotidyltransferase-related domain is directly involved in the GDP/GTP exchange, whereas the C-terminal conserved domain may be involved in the interaction of eIF-2B, eIF-4 gamma, and eIF-5 with eIF-2.

MeSH terms

  • Amino Acid Sequence
  • Conserved Sequence*
  • DNA-Binding Proteins*
  • Eukaryotic Initiation Factor-2B
  • Fungal Proteins / chemistry
  • Guanine Nucleotide Exchange Factors
  • Molecular Sequence Data
  • Nucleotidyltransferases / chemistry
  • Protein Kinases / chemistry
  • Proteins / chemistry*
  • Repressor Proteins / chemistry
  • Saccharomyces cerevisiae / chemistry*
  • Saccharomyces cerevisiae Proteins*


  • DNA-Binding Proteins
  • Eukaryotic Initiation Factor-2B
  • Fungal Proteins
  • GCD6 protein, S cerevisiae
  • Guanine Nucleotide Exchange Factors
  • Proteins
  • Repressor Proteins
  • Saccharomyces cerevisiae Proteins
  • Protein Kinases
  • Nucleotidyltransferases