Dynamic interaction network involving the conserved intrinsically disordered regions in human eIF5

Biophys Chem. 2021 Dec 10;281:106740. doi: 10.1016/j.bpc.2021.106740. Online ahead of print.ABSTRACTTranslation initiation in eukaryotes requires multiple eukaryotic translation initiation factors (eIFs) and involves continuous remodeling of the ribosomal preinitiation complex (PIC). The GTPase eIF2 brings the initiator Met-tRNAi to the PIC. Upon start codon selection and GTP hydrolysis, promoted by eIF5, eIF2-GDP is released in complex with eIF5. Here, we report that two intrinsically disordered regions (IDRs) in eIF5, the DWEAR motif and the C-terminal tail (CTT) dynamically contact the folded C-terminal domain (CTD) and compete with each other. The eIF5-CTD•CTT interaction favors eIF2β binding to eIF5-CTD, whereas the eIF5-CTD•DWEAR interaction favors eIF1A binding, which suggests how intramolecular contact rearrangement could play a role in PIC remodeling. We show that eIF5 phosphorylation by CK2, which is known to stimulate translation and cell proliferation, significantly increases the eIF5 affinity for eIF2. Our results also indicate that the eIF2β subunit has at least two, and likely three eIF5-binding sites.PMID:34923394 | DOI:10.1016/j.bpc.2021.106740

Source: Biophysical Chemistry - December 19, 2021 Category: Chemistry Authors: Eleanor Elise Paul Kay Ying Lin Nathan Gamble Amy Wei-Lun Tsai Simon H K Swan Yu Yang Matthew Doran Assen Marintchev Source Type: research