Kinetic Analysis of Late Steps of Eukaryotic Translation Initiation

Michael G. Acker, Byung Sik Shin, Jagpreet S. Nanda, Adesh K. Saini, Thomas E. Dever, Jon R. Lorsch

Research output: Contribution to journalArticlepeer-review

49 Scopus citations


Little is known about the molecular mechanics of the late events of translation initiation in eukaryotes. We present a kinetic dissection of the transition from a preinitiation complex after start codon recognition to the final 80S initiation complex. The resulting framework reveals that eukaryotic initiation factor (eIF)5B actually accelerates the rate of ribosomal subunit joining, and this acceleration is influenced by the conformation of the GTPase active site of the factor mediated by the bound nucleotide. eIF1A accelerates joining through its C-terminal interaction with eIF5B, and eIF1A release from the initiating ribosome, which occurs only after subunit joining, is accelerated by GTP hydrolysis by eIF5B. Following subunit joining, GTP hydrolysis by eIF5B alters the conformation of the final initiation complex and clears a path to promote rapid release of eIF1A. Our data, coupled with previous work, indicate that eIF1A is present on the ribosome throughout the entire initiation process and plays key roles at every stage.

Original languageEnglish (US)
Pages (from-to)491-506
Number of pages16
JournalJournal of molecular biology
Issue number2
StatePublished - Jan 16 2009
Externally publishedYes


  • eIF1A
  • eIF5B
  • eukaryotic translation initiation
  • protein synthesis
  • subunit joining

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology


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