Multiple roles for the C-terminal domain of elF5 in translation initiation complex assembly and GTPase activation

Academic Article


  • eIF5 stimulates the GTPase activity of eIF2 bound to Met-tRNAiMet, and its C-terminal domain (eIF5-CTD) bridges interaction between eIF2 and eIF3/eIF1 in a multifactor complex containing Met-tRNAiMet. The tif5-7A mutation in eIF5-CTD, which destabilizes the multifactor complex in vivo, reduced the binding of Met-tRNAiMet and mRNA to 40S subunits in vitro. Interestingly, eIF5-CTD bound simultaneously to the eIF4G subunit of the cap-binding complex and the NIP1 subunit of eIF3. These interactions may enhance association of eIF4G with eIF3 to promote mRNA binding to the ribosome. In vivo, tif5-7A eliminated eIF5 as a stable component of the pre-initiation complex and led to accumulation of 48S complexes containing eIF2; thus, conversion of 48S to 80S complexes is the rate-limiting defect in this mutant. We propose that eIF5-CTD stimulates binding of Met-tRNAiMet and mRNA to 40S subunits through interactions with eIF2, eIF3 and eIF4G; however, its most important function is to anchor eIF5 to other components of the 48S complex in a manner required to couple GTP hydrolysis to AUG recognition during the scanning phase of initiation.
  • Authors

    Digital Object Identifier (doi)

    Author List

  • Asano K; Shalev A; Phan L; Nielsen K; Clayton J; Valášek L; Donahue TF; Hinnebusch AG
  • Start Page

  • 2326
  • End Page

  • 2337
  • Volume

  • 20
  • Issue

  • 9