J. Marcotrigiano et al., Cap-dependent translation initiation in eukaryotes is regulated by a molecular mimic of elF4G, MOL CELL, 3(6), 1999, pp. 707-716
elF4G uses a conserved Tyr-X-X-X-X-Leu-phi segment (where X is variable and
phi is hydrophobic) to recognize elF4E during cap-dependent translation in
itiation in eukaryotes. High-resolution X-ray crystallography and complemen
tary biophysical methods have revealed that this elF4E recognition motif un
dergoes a disorder-to-order transition, adopting an L-shaped, extended chai
n/alpha-helical conformation when it interacts with a phylogenetically inva
riant portion of the convex surface of elF4E. Inhibitors of translation ini
tiation known as elF4E-binding proteins (4E-BPs) contain similar elF4E reco
gnition motifs. These molecules are molecular mimics of elF4G, which act by
occupying the same binding site on the convex dorsum of elF4E and blocking
assembly of the translation machinery. The implications of our results for
translation initiation are discussed in detail, and a molecular mechanism
for relief of translation inhibition following phosphorylation of the 4E-BP
s is proposed.