X-ray structures of the universal translation initiation factor IF2/eIF5B: conformational changes on GDP and GTP binding

Abstract

X-ray structures of the universal translation initiation factor IF2/eIF5B have been determined in three states: free enzyme, inactive IF2/eIF5B-GDP, and active IF2/eIF5B-GTP. IF2/eIF5B is a conserved GTPase that facilitates ribosomal subunit joining and Met-tRNAi binding to ribosomes in all three kingdoms of life. The 'chalice-shaped' protein consists of an N-terminal G domain (I), plus and EF-Tu-type -barrel (II) followed by a novel //sandwich (III) connected via a long -helix to a second EF-Tu-type -barrel (IV). Structural comparisons reveal a molecular lever, which amplifies a modest conformational change in the Switch 2 region of the G domain induced by Mg 2+ /GTP binding over a distance of 90 from the G domain active center to domain IV. IF2/eIF5B interacts with eIF1A through its C-terminal -barrel domain. This region is critical for growth in vivo and translation in vitro.