Translation initiation is a sophisticated, well regulated and highly coordinated cellular process in eukaryotes, in which at least 11 eukayrotic initiation factors (eIFs) are included. The W2 domain (two invariant tryptophans) is a region of ~165 amino acids which is found in the C terminus of the following eIFs [ (PUBMED:8520487) (PUBMED:10958635) (PUBMED:14681227) (PUBMED:16616930) (PUBMED:16781736) ]:
Eukaryotic translation initiation factor 5 (eIF-5), a GTPase-activating protein (GAP) specific for eIF2.
The W2 domain has a globular fold and is exclusively composed out of alpha- helices [ (PUBMED:14681227) (PUBMED:16616930) (PUBMED:16781736) ]. The structure can be divided into a structural C-terminal core onto which the two N-terminal helices are attached. The core contains two aromatic/acidic residue-rich regions (AA boxes), which are important for mediating protein-protein interactions.
Multidomain organization of eukaryotic guanine nucleotide exchange translation initiation factor eIF-2B subunits revealed by analysis of conserved sequence motifs.
Protein Sci. 1995; 4: 1608-17
Display abstract
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.
