eIF5 is a dual function GAP and GDI for eukaryotic translational control

Abstract

We recently showed in a publication in Nature that the eukaryotic translation initiation factor eIF5 has a second regulatory function and is a GDI (GDP dissociation inhibitor) in addition to its previously characterized role as a GAP (GTPase accelerating protein). These findings provide new insight into the mechanism of translation initiation in eukaryotic cells. Additional findings show that the GDI function is critical for the normal regulation of protein synthesis by phosphorylation of eIF2α at ser51. Because eIF2 phosphorylation is a ubiquitous mode of translational control these results are of broad interest. Here we review these and related studies and suggest they offer further evidence of parallels between the functions of regulators of the translation factor eIF 2 and both heterotrimeric and small GTPases.

Figure 1

GAP and GDI functions of eIF5 during translation initiation. (A) The eIF2 G-protein cycle is central to translation initiation. (B) Domain structure of eIF5 and related functions. Relevant mutations and functional impacts described in the text are indicated. Structural cartoons were created with PyMol (http://www.pymol.org/) using PDB IDs 2E9H and 2FUL. (C) The GoLoco and eIF5 DWEAR motifs. Alignments were taken from Pfam (http://pfam.sanger.ac.uk/) and motifs logos were generated using WebLogo (http://weblogo.berkeley.edu/).