Structure of eIF3b RNA Recognition Motif and Its Interaction with eIF3j

International audience ; Mammalian eIF3 is a 700-kDa multiprotein complex essential for initiation of protein synthesis in eukaryotic cells. It consists of 13 subunits (eIF3a to-m), among which eIF3b serves as a major scaffolding protein. Here we report the solution structure of the N-terminal RNA recognition motif of human eIF3b (eIF3b-RRM) determined by NMR spectroscopy. The structure reveals a noncanonical RRM with a negatively charged surface in the-sheet area contradictory with potential RNA binding activity. Instead, eIF3j, which is required for stable 40 S ribo-some binding of the eIF3 complex, specifically binds to the rear-helices of the eIF3b-RRM, opposite to its-sheet surface. Moreover, we identify that an N-terminal 69-amino acid peptide of eIF3j is sufficient for binding to eIF3b-RRM and that this interaction is essential for eIF3b-RRM recruitment to the 40 S riboso-mal subunit. Our results provide the first structure of an important subdomain of a core eIF3 subunit and detailed insights into protein protein interactions between two eIF3 subunits required for stable eIF3 recruitment to the 40 S subunit.