EIF4B is characterized by a single foldedRNA recognition motif (RRM) near itsN-terminus, which adopts a classical beta alpha beta beta alpha beta topology. This RRM is responsible for RNA binding but interacts with RNA relatively weakly on its own; high-affinity binding is facilitated by adjacent N- andC-terminal extensions. The majority of the EIF4B protein, encompassing roughly 400 amino acids downstream of the RRM, isintrinsically disordered and forms what is known as the intrinsically disordered region (IDR). This IDR does not adopt a stable three-dimensional structure but instead enables dynamic interactions, self-association, and the formation of large oligomers and biomolecular condensates under certain cellular conditions. A short helical segment within the IDR, coinciding with an arginine-rich motif (ARM), further contributes to RNA binding.[6][7]
Mammalian eIF4B acts as a dimer, and other studies had shown that it could form higher-order oligomers as well, through intrinsically disordered regions (IDR).[7]
Eukaryotic translation initiation factor 4B (EIF4B) is a multidomain protein essential for efficientcap-dependent translation in eukaryotic cells. Structurally, EIF4B contains a single foldedRNA recognition motif (RRM) near its N-terminus.[6][8][9] This RRM is responsible for RNA binding but interacts with RNA relatively weakly on its own; high-affinity binding is facilitated by adjacent N- and C-terminal extensions.[6][10] The majority of the EIF4B protein, encompassing roughly 400 amino acids downstream of the RRM, is intrinsically disordered and forms what is known as the intrinsically disordered region (IDR).[7] This IDR does not adopt a stable three-dimensional structure but instead enables dynamic interactions, self-association, and the formation of large oligomers and biomolecular condensates under certain cellular conditions.[7] A short helical segment within the IDR, coinciding with an arginine-rich motif (ARM), further contributes to RNA binding.[7] The flexible and highly dynamic nature of the IDR allows EIF4B to orchestrate diverse molecular interactions critical for translation initiation, including stimulation of the helicase activity of eIF4A and supporting the assembly of other components of the translation initiation machinery.[11]
EIF4B is a critical protein in the process of cap-dependent translation initiation in eukaryotic cells. Its primary function is to enhance the helicase activity of eIF4A, a DEAD-box RNA helicase, by stimulating its ability to unwind secondary structures in the 5′ untranslated regions (UTRs) of mRNAs[9].[11][12] This unwinding activity is vital for the ribosome to scan along the mRNA and locate the start codon efficiently. eIF4B also acts as a scaffold by interacting with other translation initiation factors, such as eIF3 and eIF4F, facilitating the assembly of the translation initiation complex.[13] Furthermore, eIF4B’s RNA binding capacity—mediated both by its RNA recognition motif (RRM) and its arginine-rich motif (ARM)—directly supports the recruitment and stabilization of mRNA on the ribosome, ensuring efficient and accurate initiation of protein synthesis.[6][10] The multifaceted functions of eIF4B are essential for regulating translational output and adapting protein synthesis to cellular conditions.[14]
eIF4B has been shown tointeract with and stimulate the enzymatic/RNA helicase activity ofeIF4A, also increasing its RNA and ATP binding activity, and bind to theeIF3 complex through theeIF3A subunit.[15] This interaction results in the recruitment of theeukaryotic small ribosomal subunit (40S) to the mRNA which will in turn set the stage for the later steps leading toelongation.
eIF4B is overexpressed in cancer cells and certain studies had named eIF4B as a potential therapeutic target for treatment of certain types of cancer.[16]
Maruyama K, Sugano S (Jan 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides".Gene.138 (1–2):171–174.doi:10.1016/0378-1119(94)90802-8.PMID8125298.
Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (Oct 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library".Gene.200 (1–2):149–156.doi:10.1016/S0378-1119(97)00411-3.PMID9373149.
