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.