eIF1A/eIF5B interaction network and its functions in translation initiation complex assembly and remodeling.
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.
Boston University School of Medicine, Department of Physiology and Biophysics, Boston, MA 02118, USA.
Nabanita
N
Nag
Boston University School of Medicine, Department of Physiology and Biophysics, Boston, MA 02118, USA.
Kai Ying
KY
Lin
Indiana University, Department of Chemistry, Bloomington, IN 47405, USA.
Katherine A
KA
Edmonds
Boston University School of Medicine, Department of Physiology and Biophysics, Boston, MA 02118, USA.
Jielin
J
Yu
Boston University School of Medicine, Department of Physiology and Biophysics, Boston, MA 02118, USA.
Devika
D
Nadkarni
Bridgewater State University, Department of Biological Sciences, Bridgewater, MA 02325, USA.
Boriana
B
Marintcheva
Boston University School of Medicine, Department of Physiology and Biophysics, Boston, MA 02118, USA amarint@bu.edu.
Assen
A
Marintchev
D001665:Binding Sites; D015977:Eukaryotic Initiation Factor-1 / Q000378:metabolism*; D039642:Eukaryotic Initiation Factors / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D008958:Models, Molecular; D046912:Multiprotein Complexes / Q000737:chemistry / Q000378:metabolism; D010442:Peptide Chain Initiation, Translational / Q000502:physiology*; D011485:Protein Binding; D000072417:Protein Domains; D012270:Ribosomes / Q000737:chemistry / Q000378:metabolism; D012996:Solutions
D015977:Eukaryotic Initiation Factor-1; D039642:Eukaryotic Initiation Factors; D046912:Multiprotein Complexes; D012996:Solutions; C451459:eukaryotic initiation factor-5B; C026022:eukaryotic peptide initiation factor-1A