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Publication Abstract from PubMed

The heterotrimeric GTPase eukaryotic translation initiation factor 2 (eIF2) delivers the initiator Met-tRNAi to the ribosomal translation preinitiation complex (PIC). eIF2beta has three lysine-rich repeats (K-boxes), important for binding to the GTPase-activating protein eIF5, the guanine nucleotide exchange factor eIF2B, and the regulator eIF5-mimic protein (5MP). Here, we combine X-ray crystallography with NMR to understand the molecular basis and dynamics of these interactions. The crystal structure of yeast eIF5-CTD in complex with eIF2beta K-box 3 reveals an extended binding site on eIF2beta, far beyond the K-box. We show that eIF2beta contains three distinct binding sites, centered on each of the K-boxes, and that human eIF5, eIF2Bepsilon, and 5MP1 can bind to all three sites. Our results reveal how eIF2B speeds up the dissociation of eIF5 from eIF2-GDP to promote nucleotide exchange; and how 5MP1 can destabilize eIF5 binding to eIF2 and the PIC, to promote stringent start codon selection. All these affinities are increased by CK2 phosphomimetic mutations, highlighting the role of CK2 in both remodeling and stabilizing the translation apparatus.

Molecular basis for the interactions of eIF2beta with eIF5, eIF2B, and 5MP1 and their regulation by CK2.,Wagner PA, Song M, Doran P, Seker A, Ficner R, Kuhle B, Marintchev A RNA. 2025 Jul 16:rna.080652.125. doi: 10.1261/rna.080652.125. PMID:40670154^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.