Molecular basis for the interactions of eIF2β with eIF5, eIF2B, and 5MP1 and their regulation by CK2.

ABSTRACT: The heterotrimeric GTPase eukaryotic translation initiation factor 2 (eIF2) delivers the initiator Met-tRNA_i 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 r

SUBMITTER: Wagner PA 

PROVIDER: S-EPMC12439599 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature