eIF4G and CBP80 share a common origin and similar domain organization: implications for the structure and function of eIF4G.
Eukaryotic translation initiation factor 4G (eIF4G) plays a critical role in protein expression, and is at the center of a complex regulatory network. Together with the cap-binding protein eIF4E, it recruits the small ribosomal subunit to the 5'-end of mRNA and promotes the assembly of a functional translation initiation complex, which scans along the mRNA to the translation start codon. Human eIF4G contains three consecutive HEAT domains, as well as long unstructured regions involved in multiple protein-protein interactions. Despite the accumulating data about the structure and function of eIF4G, the mechanisms of coordination and regulation of its interactions with other factors have remained largely unknown. Here, we present evidence that eIF4G and the large subunit of the nuclear cap-binding complex, CBP80, share a common origin and domain structure. We propose that the organization of the individual domains in eIF4G and CBP80 could also be conserved. The structure of CBP80, in complex with the nuclear cap-binding protein CBP20, is used to build a model for the mutual orientation of the domains in eIF4G and their interactions with other factors. The organization of the CBP80-CBP20 complex suggests how the activity of eIF4G in translation initiation could be regulated through a dynamic network of overlapping intra- and intermolecular interactions centered around the eIF4G HEAT domains.
Marintchev
Assen
A
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 240 Longwood Avenue, Boston, Massachusetts 02115, USA.
Wagner
Gerhard
G
D000818:Animals; D039603:Eukaryotic Initiation Factor-4G / Q000737:chemistry*; D039642:Eukaryotic Initiation Factors / Q000737:chemistry; D006801:Humans; D008958:Models, Molecular; D039502:Nuclear Cap-Binding Protein Complex / Q000737:chemistry*; D017433:Protein Structure, Secondary; D012333:RNA, Messenger / Q000235:genetics
D039603:Eukaryotic Initiation Factor-4G; D039642:Eukaryotic Initiation Factors; D039502:Nuclear Cap-Binding Protein Complex; D012333:RNA, Messenger