Aminoacylation complex structures of leucyl-tRNA synthetase and tRNALeu reveal two modes of discriminator-base recognition.
Leucyl-tRNA synthetase (LeuRS) specifically recognizes the characteristic long variable arm and the discriminator base, A73, of tRNA(Leu) in archaea and eukarya. The LeuRS 'editing domain' hydrolyzes misformed noncognate aminoacyl-tRNA. Here we report the crystal structure of the archaeal Pyrococcus horikoshii LeuRS-tRNA(Leu) complex. The protruding C-terminal domain of LeuRS specifically recognizes the bases at the tip of the long variable arm. The editing domain swings from its tRNA-free position to avoid clashing with the tRNA. Consequently the tRNA CCA end can bend and reach the aminoacylation active site. The tRNA 3' region assumes two distinct conformations that allow A73 to be specifically recognized in different ways. One conformation is the canonical 'aminoacylation state.' The other conformation seems to be the 'intermediate state,' where the misaminoacylated 3' end has partially relocated to the editing domain.
Fukunaga
Ryuya
R
Department of Biophysics and Biochemistry, Graduate School of Science, The University of Tokyo, Tokyo, Japan.
Yokoyama
Shigeyuki
S
D000595:Amino Acid Sequence; D001483:Base Sequence; D018360:Crystallography, X-Ray; D007935:Leucine-tRNA Ligase / Q000737:chemistry* / Q000378:metabolism; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D009711:Nucleotides / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation; D043902:Pyrococcus horikoshii / Q000201:enzymology* / Q000235:genetics; D012356:RNA, Transfer, Leu / Q000737:chemistry* / Q000378:metabolism; D046249:Transfer RNA Aminoacylation
D009711:Nucleotides; D012356:RNA, Transfer, Leu; D007935:Leucine-tRNA Ligase