X-ray structures of the universal translation initiation factor IF2/elF5B: Conformational changes on GDP and GTP binding

X-ray structures of the universal translation initiation factor IF2/eIF5B have been determined in three stales: free enzyme, inactive IF2/eIF5B.GDP, and active IF2/eIF5B.GTP. The chalice-shaped enzyme is a GTPase that facilitates ribosomal subunit joining and Met-tRNA(i) binding to ribosomes in all three kingdoms of life. The conserved core of IF2/eIF5B consists of an N-terminal G domain (I) plus an EF-Tu-type beta barrel (II), followed by a novel alpha/beta/alpha -sandwich (III) connected via an alpha helix to a second EF-Tu-type beta 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 Mg2+/GTP binding over a distance of 90 Angstrom from the G domain active center to domain IV. Mechanisms of GTPase function and ribosome binding are discussed.