Recognition of γ-Subunit by β-Subunit in Translation Initiation Factor 2. Stabilization of the GTP-Bound State of I/F 2 in Archaea and Eukaryotes

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Oleg S. Nikonov^1,a*, Ekaterina Yu. Nikonova¹, Anastasiia G. Tarabarova¹, Alisa O. Mikhaylina¹, Olesya V. Kravchenko¹, Natalia A. Nevskaya¹, and Stanislav V. Nikonov¹

¹Institute of Protein Research, Russian Academy of Sciences, 142290 Pushchino, Moscow Region, Russia

^* To whom correspondence should be addressed.

Received October 26, 2022; Revised January 27, 2023; Accepted January 28, 2023

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Eukaryotic and archaeal translation initiation factor 2 (e/aIF2) functions as a heterotrimeric complex. It consists of three subunits (α, β, γ). α- and β-subunits are bound to γ-subunit by hydrogen bonds and van der Waals interactions, but do not contact each other. Although 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 introduced mutations in the recognition part of the βγ interface and showed that hydrophobic effect plays a crucial role in the recognition of subunits both in eukaryotes and archaea. Shape and properties of the groove on the surface of γ-subunit facilitates transition of the disordered recognition part of the β-subunit into an 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, transition of the γ-subunit to the active state leads to additional contact between the region of switch 1 and C-terminal part of the β-subunit, which stabilizes helical conformation of the switch.

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KEY WORDS: translation initiation factor 2, structure, βγ recognition

DOI: 10.1134/S0006297923020062

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