Eukaryotic translation initiation is a highly regulated process involving multiple steps, from 43S pre-initiation complex (PIC) assembly, to ribosomal subunit joining. Subunit joining is controlled by the G-protein eukaryotic translation initiation factor 5B (eIF5B). Another protein, eIF1A, is involved in virtually all steps, including subunit joining. The intrinsically disordered eIF1A C-terminal tail (eIF1A-CTT) binds to eIF5B Domain-4 (eIF5B-D4). The ribosomal complex undergoes conformational rearrangements at every step of translation initiation; however, the underlying molecular mechanisms are poorly understood. Here we report three novel interactions involving eIF5B and eIF1A: (i) a second binding interface between eIF5B and eIF1A; (ii) a dynamic intramolecular interaction in eIF1A between the folded domain and eIF1A-CTT; and (iii) an intramolecular interaction between eIF5B-D3 and -D4. The intramolecular interactions within eIF1A and eIF5B interfere with one or both eIF5B/eIF1A contact interfaces, but are disrupted on the ribosome at different stages of translation initiation. Therefore, our results indicate that the interactions between eIF1A and eIF5B are being continuously rearranged during translation initiation. We present a model how the dynamic eIF1A/eIF5B interaction network can promote remodeling of the translation initiation complexes, and the roles in the process played by intrinsically disordered protein segments.
Nag, N., Lin, K.Y., Edmonds, K.A., Yu, J., Nadkarni, D., Marintcheva, B., & Marintchev, A. (2016). eIF1A/eIF5B Interaction Network and its Functions in Translation Initiation Complex Assembly and Remodeling. Nucleic Acids Research, 44(15), 7441-7456. doi: 10.1093/nar/gkw552
Virtual Commons Citation
Nag, Nabanita; Lin, Kai Ying; Edmonds, Katherine A.; Yu, Jielin; Nadkarni, Devika; Marintcheva, Boriana; and Marintchev, Assen (2016). eIF1A/eIF5B Interaction Network and its Functions in Translation Initiation Complex Assembly and Remodeling. In Biological Sciences Faculty Publications. Paper 60.
Available at: http://vc.bridgew.edu/biol_fac/60
This article is an Open Access article distributed under the terms of a Creative Commons Attribution License 4.0.