Phenylalanyl-tRNA synthetase from Thermus thermophilus has four antiparallel folds of which only two are catalytically functional

Abstract

Phenylalanyl-tRNA synthetase from Thermus thermophilus has an alpha 2 beta 2 type quaternary structure and is one of the most complicated members of the synthetase family. Identification of PheRSTT as a member of class II aaRSs was based only on sequence alignment of the small alpha-subunit with other synthetases. The three-dimensional crystal structure of the catalytic and 'catalytic-like' domains at 2.9 A resolution in PheRSTT is described. The alpha-subunit contains an antiparallel fold which includes signature motifs 1, 2 and 3, characteristic of class II synthetases. One of the three structural domains of the beta-subunit (alpha'-domain) is formed by a seven-stranded antiparallel beta-sheet surrounded by alpha-helices similar to catalytic domains in SerRS, AspRS and the alpha-subunit of PheRSTT. The alpha beta heterodimer (alpha and alpha') exhibits essentially the same topology in the intersubunit region as in the known alpha 2 structures of class II aaRS's. The multimerization area of whole PheRSTT molecule comprises a quasi-tetrahedral four-helix bundle.