9F79

Crystal structure of the S. cerevisiae eIF2beta N-terminal tail bound to the C-terminal domain of eIF5

Summary for 9F79

• Entry DOI: 10.2210/pdb9f79/pdb
• Descriptor: Eukaryotic translation initiation factor 5, Eukaryotic translation initiation factor 2 subunit beta (3 entities in total)
• Functional Keywords: translation, eukaryotic translation initiation factor, complex, eif5, w2 domain, eif2 beta
• Biological source: Saccharomyces cerevisiae (brewer's yeast); More
• Total number of polymer chains: 3
• Total formula weight: 55551.37

Authors

Kuhle, B.,Marintchev, A.,Ficner, R. (deposition date: 2024-05-03, release date: 2025-09-03, Last modification date: 2025-10-01)

Primary citation

Wagner, P.A.,Song, M.,Doran, P.,Seker, A.,Ficner, R.,Kuhle, B.,Marintchev, A.
Molecular basis for the interactions of eIF2 beta with eIF5, eIF2B, and 5MP1 and their regulation by CK2.
Rna, 31:1419-1435, 2025

PubMed Abstract: The heterotrimeric GTPase eukaryotic translation initiation factor 2 (eIF2) delivers the initiator Met-tRNAi to the ribosomal translation preinitiation complex (PIC). eIF2β 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 eIF2β K-box 3 reveals an extended binding site on eIF2β, far beyond the K-box. We show that eIF2β contains three distinct binding sites, centered on each of the K-boxes, and that human eIF5, eIF2Bε, 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.

PubMed: 40670154
DOI: 10.1261/rna.080652.125

Experimental method

X-RAY DIFFRACTION (2 Å)