title: Structure of eIF3b RNA recognition motif and its interaction with eIF3j: structural insights into the recruitment of eIF3b to the 40 S ribosomal subunit.
abstract: 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 beta-sheet area contradictory with potential RNA binding activity. Instead, eIF3j, which is required for stable 40 S ribosome binding of the eIF3 complex, specifically binds to the rear alpha-helices of the eIF3b-RRM, opposite to its beta-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 ribosomal 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.
authors.affiliation: Laboratory of Molecular Biology, Medical Research Council, Hills Road, Cambridge CB2 2QH, United Kingdom.
authors.forename: Latifa
authors.initials: L
authors.lastname: ElAntak
authors.forename: Andreas G
authors.initials: AG
authors.lastname: Tzakos
authors.forename: Nicolas
authors.initials: N
authors.lastname: Locker
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Lukavsky
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D039621:Eukaryotic Initiation Factor-3 / Q000737:chemistry*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D010448:Peptide Initiation Factors / Q000737:chemistry; D011485:Protein Binding; D014176:Protein Biosynthesis; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012270:Ribosomes / Q000737:chemistry; D017386:Sequence Homology, Amino Acid
chemical_list: D039621:Eukaryotic Initiation Factor-3; D010448:Peptide Initiation Factors