The joining of ribosomal subunits in eukaryotes requires eIF5B

Nature. 2000 Jan 20;403(6767):332-5. doi: 10.1038/35002118.


Initiation of eukaryotic protein synthesis begins with the ribosome separated into its 40S and 60S subunits. The 40S subunit first binds eukaryotic initiation factor (eIF) 3 and an eIF2-GTP-initiator transfer RNA ternary complex. The resulting complex requires eIF1, eIF1A, eIF4A, eIF4B and eIF4F to bind to a messenger RNA and to scan to the initiation codon. eIF5 stimulates hydrolysis of eIF2-bound GTP and eIF2 is released from the 48S complex formed at the initiation codon before it is joined by a 60S subunit to form an active 80S ribosome. Here we show that hydrolysis of eIF2-bound GTP induced by eIF5 in 48S complexes is necessary but not sufficient for the subunits to join. A second factor termed eIF5B (relative molecular mass 175,000) is essential for this process. It is a homologue of the prokaryotic initiation factor IF2 (re and, like it, mediates joining of subunits and has a ribosome-dependent GTPase activity that is essential for its function.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Catalysis
  • Codon, Initiator
  • Eukaryotic Initiation Factor-1 / metabolism
  • Eukaryotic Initiation Factor-2 / metabolism
  • Eukaryotic Initiation Factor-3
  • Eukaryotic Initiation Factor-5
  • GTP Phosphohydrolases / metabolism
  • Guanosine Triphosphate / metabolism
  • Guanylyl Imidodiphosphate / metabolism
  • Humans
  • Hydrolysis
  • Molecular Sequence Data
  • Peptide Chain Initiation, Translational*
  • Peptide Initiation Factors / metabolism*
  • Puromycin / analogs & derivatives*
  • Puromycin / biosynthesis
  • RNA, Messenger / metabolism
  • Recombinant Proteins / metabolism
  • Ribosomes / metabolism*


  • Codon, Initiator
  • Eukaryotic Initiation Factor-1
  • Eukaryotic Initiation Factor-2
  • Eukaryotic Initiation Factor-3
  • Eukaryotic Initiation Factor-5
  • Peptide Initiation Factors
  • RNA, Messenger
  • Recombinant Proteins
  • eukaryotic peptide initiation factor-1A
  • Guanylyl Imidodiphosphate
  • Puromycin
  • methionylpuromycin
  • Guanosine Triphosphate
  • GTP Phosphohydrolases