title: Mapping the binding interface between human eukaryotic initiation factors 1A and 5B: a new interaction between old partners.
abstract: The translation initiation factors (IFs) IF1/eIF1A and IF2e/IF5B have been conserved throughout all kingdoms. Although the central roles of the bacterial factors IF1 and IF2 were established long ago, the importance of their eukaryotic homologs, eukaryotic IFs (eIFs) eIF1A and eIF5B, has only recently become evident. The translation machinery in eukaryotes is more complex and accordingly, eIF1A and eIF5B seem to have acquired a number of new functions while also retaining many of the roles of bacterial IF1 and IF2. IF1 and IF2 have been shown to interact on the ribosome but no binding has been detected for the free factors. In contrast, yeast eIF1A and eIF5B have been reported to interact in the absence of ribosomes. Here, we have identified the binding interface between human eIF1A and the C-terminal domain of eIF5B by using solution NMR. That interaction interface involves the C termini of the two proteins, which are not present in bacterial IF1 and IF2. The interaction is, therefore, unique to eukaryotes. A structural model for the interaction of eIF1A and eIF5B in the context of the ribosome is presented. We propose that eIF1A and eIF5B simultaneously interact at two sites that are >50 A apart: through their C termini as reported here, and through an interface previously identified in bacterial IF1 and IF2. The binding between the C termini of eIF1A and eIF5B has implications for eukaryote-specific mechanisms of recruitment and release of translation IFs from the ribosome.
authors.affiliation: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Building C1, Room 112, 240 Longwood Avenue, Boston, MA 02115, USA.
authors.forename: Assen
authors.initials: A
authors.lastname: Marintchev
authors.forename: Victoria G
authors.initials: VG
authors.lastname: Kolupaeva
authors.forename: Tatyana V
authors.initials: TV
authors.lastname: Pestova
authors.forename: Gerhard
authors.initials: G
authors.lastname: Wagner
mesh_terms: D001665:Binding Sites; D015977:Eukaryotic Initiation Factor-1; D040061:Eukaryotic Initiation Factor-5 / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D010448:Peptide Initiation Factors / Q000378:metabolism*; D011485:Protein Binding
chemical_list: D015977:Eukaryotic Initiation Factor-1; D040061:Eukaryotic Initiation Factor-5; D010448:Peptide Initiation Factors; C026022:eukaryotic peptide initiation factor-1A