InterPro domain: IPR003307

Translation initiation is a sophisticated, well regulated and highlycoordinated cellular process in eukaryotes, in which at least 11 eukayroticinitiation factors (eIFs) are included. The W2 domain (two invarianttryptophans) is a region of ~165 amino acids which is found in the C terminusof the following eIFs [ 1 , 2 , 3 , 4 , 5 ]:

• Eukaryotic translation initiation factor 2B epsilon (eIF-2B-epsilon).
• Eukaryotic translation initiation factor 4 gamma (eIF-4-gamma).
• 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 [ 6 , 6 , 6 ]. The structure can be divided into a structuralC-terminal core onto which the two N-terminal helices are attached. The corecontains two aromatic/acidic residue-rich regions (AA boxes), which areimportant for mediating protein-protein interactions.

1. Multidomain organization of eukaryotic guanine nucleotide exchange translation initiation factor eIF-2B subunits revealed by analysis of conserved sequence motifs. Protein Sci. 4, 1608-17
2. Eukaryote-specific domains in translation initiation factors: implications for translation regulation and evolution of the translation system. Genome Res. 10, 1172-84
3. Structure of the catalytic fragment of translation initiation factor 2B and identification of a critically important catalytic residue. J. Biol. Chem. 279, 10584-92
4. Crystal structure of the C-terminal domain of S.cerevisiae eIF5. J. Mol. Biol. 359, 1-9
5. The crystal structure of the carboxy-terminal domain of human translation initiation factor eIF5. J. Mol. Biol. 360, 457-65