The eukaryotic translation initiation factor eIF2 delivers Met-tRNA(i)(Met) to the ribosomal small subunit in GTP-bound form associated with eIF1, eIF1A, eIF3 and eIF5, and dissociates together with eIF5 as eIF5-eIF2-GDP complex from the ribosomal small subunit after formation of start codon-anticodon base pairing between Met-tRNA(i)(Met) and mRNA. The inactive form eIF2-GDP is then exchanged for the active form eIF2-GTP by eIF2B for further initiation cycle. Previous studies showed that the C-terminal domains of eIF5 (eIF5-CTD) and eIF2B epsilon (eIF2B epsilon-CTD) have a common eIF2 beta-binding site for interacting with an N-terminal region of eIF2 beta (eIF2 beta-NTD). Here we have reconstructed the complexes of (eIF5-CTD)-(eIF2 beta-NTD) and (eIF2B epsilon-CTD)-(eIF2 beta-NTD) in vitro, and investigated binding mechanism by circular dichroism spectroscopy and small angle X-ray scattering in solution. The results showed the conformation of eIF2 beta-NTD was changed when bound to partner proteins, whereas the structures of eIF beta-CTD and eIF2B epsilon-CTD were similar in both isolated and complex states. We propose that eIF2 beta-NTD works as an intrinsically disordered domain which is disorder in the isolated state, but folds into a definite structure when bound to its partner proteins. Such flexibility of eIF2 beta-NTD is expected to be responsible for its binding capability. (C) 2012 Elsevier Inc. All rights reserved.