YEAST TRANSFER RNA(ASP) RECOGNITION BY ITS COGNATE CLASS-II AMINOACYL-TRANSFER RNA-SYNTHETASE

AMINOACYL-RNA synthetases can be divided into two classes according to structural features inferred from sequence alignments1-3. This classification correlates almost perfectly with the attachment of the amino acid to the 2'-OH (class I) or 3'-OH (class II) group of the terminal adenosine4-6. Six subgroups of higher homology can be inferred from sequence analysis7,8. The five aminoacyl-tRNA synthetases whose crystal structures are known (MetRS, TyrRS and GlnRS in class I, SerRS and AspRS in class II)9-13 belong to different subgroups. Two of them, GluRS and AspRS, have been cocrystallized with their cognate tRNA11,13. AspRS, like six other members of class II, is an alpha2 dimer. Yeast tRNA(Asp) exhibits five identity determinants: the three anticodon bases, the discriminator base G73 and the base pair G10-U25(14). We report here that the refined crystal structure of AspRS complexed with TRNA(Asp) at 2.9 angstrom resolution reveals three regions of contact, each involving a domain of AspRS and at least one identity determinant of tRNA(Asp). The mode of binding of the acceptor stem of tRNA(Asp) by AspRS can be generalized to class II aminoacyl-tRNA synthetases, whereas the deciphering of the anticodon, which involves a large conformational change of the loop and the formation of a bulge, is more specific to the aspartic system.