Regulation of Translation Initiation by a Network of Overlapping Intra- and Intermolecular Interactions Mediated by Natively Unfolded Protein Segments
Translation initiation requires a number of eukaryotic translation initiation factors (eIFs) and consists of several steps: initiation complex assembly; binding to mRNA; scanning; start codon recognition; and ribosomal subunit joining. The G-protein eIF2 and its GTPase-activating protein (GAP) eIF5 play central roles in start codon recognition. A second G-protein, eIF5B promotes ribosomal subunit joining. eIF1A, is involved in virtually all steps of translation initiation. We used a combination of NMR chemical shift mapping, fluorescence spectroscopy, site-directed mutagenesis, and deletion analysis to elucidate the interplay among intra- and intermolecular interactions of human translation initiation factors eIF5B, eIF1A and eIF5. We discovered multiple transient interactions, too weak to form in isolation, but sufficient to modulate the affinity of other interactions in the context of large complexes. These interactions are often mediated by natively unfolded protein segments. A common theme emerges, where natively unfolded protein segments are able to form weak transient interactions while remaining unfolded and flexible, thus apparently limiting the entropy cost of the interaction, whereas stronger interactions require at least partial folding and immobilization of the peptide. Based on the observed overlaps in interaction surfaces and the relative binding affinities, we propose a mechanism for formation and remodeling of ribosomal complexes through coordinated rearrangement of multiple relatively weak interactions.
Marintcev, A., Nag, N., Edmonds, K., Yu, J., & Marintcheva, B., (2015). Regulation of Translation Initiation by a Network of Overlapping Intra- and Intermolecular Interactions Mediated by Natively Unfolded Protein Segments. FASEB Journal, 29(1 Supplement), 563.7.
Virtual Commons Citation
Marintchev, Assen; Nag, Nabinita; Edmonds, Katherine; Yu, Jielin; and Marintcheva, Boriana (2015). Regulation of Translation Initiation by a Network of Overlapping Intra- and Intermolecular Interactions Mediated by Natively Unfolded Protein Segments. In Biological Sciences Faculty Publications. Paper 49.
Available at: http://vc.bridgew.edu/biol_fac/49