STRUCTURE OF PheRS + tRNA COMPLEX AND NON-CANONICAL CELLULAR FUNCTIONS OF THE ENZYME

M. Safro1, Y. Goldgur1, L. Mosyak1, L.Reshetnikova2, M.Rodova1, V. Ankilova3

1 Department of Structural Biology, Weizmann Institute of Science, Rehovot, Israel
2 Institute of Molecular Biology, Moscow 117984, Russia
3 Institute of Bioorganic Chemistry, Novosibirsk 690390, Russia

Phenylalanyl-tRNA synthetase (PheRS) is a heterodimeric class II enzyme (ab)2 which is known to be among the most complex enzyme in aaRS family. Architecture of cytoplasmic PheRS's is markedly conserved during evolution from prokaryotes to eukaryotes.

Three-dimensional structure of Th. thermophilus PheRS [1] and its complex with cognate tRNAPhe [2] displays that ab heterodimer consists of eleven structural domains. Whereas a-subunit domains are characteristic of class II aaRSs and create catalytic module and coiled-coil domain directly involved in aminoacylation and tRNAPhe binding, b-subunit reveals a collection of structural domains which are likely to perform various functions in other proteins.

Significant structural similarities between b-subunit of Th. thermophilus PheRS and the biotin synthetase repressor protein (BirA) was observed [3]. This similarity provides an example in which all domains of one multidomain protein (BirA) appear to be constituents of the other multidomain protein (PheRS). Drawing analogy with BirA it was hypothesized [3], that PheRS also serves as a transcriptional regulator. Recently direct experiments on prokaryotic [4] and eukaryotic [5] PheRSs provide an evidence in favor of this hypothesis. Thus PheRS is involved in regulatory cellular processes not related to aminoacylation.

  1. Mosyak, L., Reshetnikova, L., Goldgur, Y., Delarue,M. & Safro, M. (1995). Structure of Phenylalanyl-tRNA synthetase from Th. thermophilus. Nat. Struct. Biol. 2, 537-547
  2. Goldgur, Y., Mosyak, L., Reshetnikova, L., Ankilova, V., Lavrik, O., Khodyreva, S. & Safro, M. (1997). The crystal structure of Phenylalanyl-tRNA synthetase from Th. thermophilus complexed with cognate tRNAPhe . Structure 5, 59-68.
  3. Safro, M. & Mosyak, L. (1995). Structural similarities in the noncatalytic domains of phenylalanyl-tRNA and biotin synthetases. Protein Science 4, 2429-2432
  4. Lechler, L., Kreutzer, R. (1998). The Phenylalanyl-tRNA Synthetase Specifically Binds DNA. J. Mol. Biol., 278, 897-901
  5. Rodova, M., Ankilova, V. & Safro, M. (1998). Human Phenylalanyl-tRNA synthetase reveals different tRNA binding mode and non-canonical cellular functions. Submitted for publication.