New insights into the interactions of the translation initiation factor 2 from archaea with guanine nucleotides and initiator tRNA

J Mol Biol. 2007 Oct 19;373(2):328-36. doi: 10.1016/j.jmb.2007.07.048. Epub 2007 Aug 2.


Heterotrimeric a/eIF2alphabetagamma (archaeal homologue of the eukaryotic translation initiation factor 2 with alpha, beta and gamma subunits) delivers charged initiator tRNA (tRNAi) to the small ribosomal subunit. In this work, we determined the structures of aIF2gamma from the archaeon Sulfolobus solfataricus in the nucleotide-free and GDP-bound forms. Comparison of the free, GDP and Gpp(NH)p-Mg2+ forms of aIF2gamma revealed a sequence of conformational changes upon GDP and GTP binding. Our results show that the affinity of GDP to the G domain of the gamma subunit is higher than that of Gpp(NH)p. In analyzing a pyrophosphate molecule binding to domain II of the gamma subunit, we found a cleft that is very suitable for the acceptor stem of tRNA accommodation. It allows the suggestion of an alternative position for Met-tRNA i Met on the alphagamma intersubunit dimer, at variance with a recently published one. In the model reported here, the acceptor stem of the tRNAi is approximately perpendicular to that of tRNA in the ternary complex elongation factor Tu-Gpp(NH)p-tRNA. According to our analysis, the elbow and T stem of Met-tRNA i Met in this position should make extensive contact with the alpha subunit of aIF2. Thus, this model is in good agreement with experimental data showing that the alpha subunit of aIF2 is necessary for the stable interaction of aIF2gamma with Met-tRNA i Met.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Archaeal Proteins / chemistry*
  • Archaeal Proteins / metabolism
  • Binding Sites
  • Guanosine Diphosphate / chemistry*
  • Guanosine Diphosphate / metabolism
  • Guanosine Triphosphate / chemistry*
  • Guanosine Triphosphate / metabolism
  • Molecular Sequence Data
  • Prokaryotic Initiation Factor-2 / chemistry*
  • Prokaryotic Initiation Factor-2 / metabolism
  • Protein Conformation
  • RNA, Transfer / chemistry
  • RNA, Transfer / metabolism
  • RNA, Transfer, Met / chemistry*
  • RNA, Transfer, Met / metabolism
  • Sulfolobus solfataricus / metabolism


  • Archaeal Proteins
  • Prokaryotic Initiation Factor-2
  • RNA, Transfer, Met
  • Guanosine Diphosphate
  • Guanosine Triphosphate
  • RNA, Transfer