Universal conservation in translation initiation revealed by human and archaeal homologs of bacterial translation initiation factor IF2.

Binding of initiator methionyl-tRNA to ribosomes is catalyzed in prokaryotes by initiation factor (IF) IF2 and in eukaryotes by eIF2. The discovery of both IF2 and eIF2 homologs in yeast and archaea suggested that these microbes possess an evolutionarily intermediate protein synthesis apparatus. We describe the identification of a human IF2 homolog, and we demonstrate by using in vivo and in vitro assays that human IF2 functions as a translation factor. In addition, we show that archaea IF2 can substitute for its yeast homolog both in vivo and in vitro. We propose a universally conserved function for IF2 in facilitating the proper binding of initiator methionyl-tRNA to the ribosomal P site.

[1]  M. Sprinzl,et al.  Initiation factors of protein biosynthesis in bacteria and their structural relationship to elongation and termination factors , 1998, Molecular microbiology.

[2]  W. Merrick,et al.  Promotion of met-tRNAiMet binding to ribosomes by yIF2, a bacterial IF2 homolog in yeast. , 1998, Science.

[3]  N. Kyrpides,et al.  Universally conserved translation initiation factors. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[4]  N. Sonenberg,et al.  A Novel Functional Human Eukaryotic Translation Initiation Factor 4G , 1998, Molecular and Cellular Biology.

[5]  P. Dennis.  Ancient Ciphers: Translation in Archaea , 1997, Cell.

[6]  Kausik Si,et al.  Function of Eukaryotic Translation Initiation Factor 1A (eIF1A) (Formerly Called eIF-4C) in Initiation of Protein Synthesis* , 1997, The Journal of Biological Chemistry.

[7]  W. Doolittle,et al.  An infB-Homolog in Sulfolobus acidocaldarius , 1996 .

[8]  E. Urcelay,et al.  Regulation of gene expression for translation initiation factor eIF-2 alpha: importance of the 3' untranslated region. , 1996, The Biochemical journal.

[9]  J. Nyborg,et al.  Structure of the ternary complex of EF-Tu: macromolecular mimicry in translation. , 1996, Trends in biochemical sciences.

[10]  A. Sachs,et al.  A common function for mRNA 5' and 3' ends in translation initiation in yeast. , 1995, Genes & development.

[11]  M. Rodnina,et al.  Site-directed mutagenesis of Thermus thermophilus elongation factor Tu. Replacement of His85, Asp81 and Arg300. , 1995, European journal of biochemistry.

[12]  H. Bussey,et al.  The nucleotide sequence of chromosome I from Saccharomyces cerevisiae. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[13]  J. Thompson,et al.  CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. , 1994, Nucleic acids research.

[14]  M. Grunberg‐Manago,et al.  In vivo study of engineered G‐domain mutants of Escherichia coli translation initiation factor IF2 , 1994, Molecular microbiology.

[15]  A. Weijland,et al.  Toward a model for the interaction between elongation factor Tu and the ribosome. , 1993, Science.

[16]  C. Gualerzi,et al.  Molecular dissection of translation initiation factor IF2. Evidence for two structural and functional domains. , 1991, The Journal of biological chemistry.

[17]  M. Grunberg‐Manago,et al.  A severely truncated form of translational initiation factor 2 supports growth of Escherichia coli. , 1991, Journal of molecular biology.

[18]  Frank McCormick,et al.  The GTPase superfamily: conserved structure and molecular mechanism , 1991, Nature.

[19]  C. Sander,et al.  Database of homology‐derived protein structures and the structural meaning of sequence alignment , 1991, Proteins.

[20]  E. Jacquet,et al.  Substitution of Val20 by Gly in elongation factor Tu. Effects on the interaction with elongation factors Ts, aminoacyl-tRNA and ribosomes. , 1989, European journal of biochemistry.

[21]  E. Jacquet,et al.  Structure‐function relationships in the GTP binding domain of EF‐Tu: mutation of Val20, the residue homologous to position 12 in p21. , 1988, The EMBO journal.

[22]  U. Maitra,et al.  Initiation factors in protein biosynthesis. , 1982, Annual review of biochemistry.