Cap-dependent translation initiation in eukaryotes is regulated by a molecular mimic of elF4G

Citation
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
Citations number
38
Categorie Soggetti
Cell & Developmental Biology
Journal title
MOLECULAR CELL
ISSN journal
10972765 → ACNP
Volume
3
Issue
6
Year of publication
1999
Pages
707 - 716
Database
ISI
SICI code
1097-2765(199906)3:6<707:CTIIEI>2.0.ZU;2-3
Abstract
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.