Recognition of γ-subunit by β-subunit. Stabilization of the GTP-bound state of translation initiation factor 2 in archaea and eukaryotes

Abstract

Eukaryotic and archaeal translation initiation factor 2 (e/aIF2) functions as a heterotrimeric complex. It consists of three subunits (α,β, γ). The α- and β-subunits are linked to the γ-subunit by hydrogen bonds and van der Waals interactions, but do not contact each other. Although the main functions of the factor are performed by the γ-subunit reliable formation of αγ- and βγ-complexes is necessary for its proper functioning. In this work, we made mutations in the recognition part of the βγ interface and showed that both in eukaryotes and archaea, the hydrophobic effect plays a decisive role in the recognition of subunits. The shape and properties of the hollow on the surface of the γ-subunit facilitates the transition of the disordered recognition part of the β-subunit into the α-helix containing approximately the same number of residues in archaea and eukaryotes. In addition, based on the newly obtained data, it was concluded that in archaea and eukaryotes, the transition of the γ-subunit to the active state leads to additional contact between its switch 1 and the C-terminal part of the β-subunit, which stabilizes the helical conformation of the switch.