Published online 23 June 2006
© 2006 The Author(s)
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Structure of human tryptophanyl-tRNA synthetase in complex with tRNATrp reveals the molecular basis of tRNA recognition and specificity
1 State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences 2 Graduate School of Chinese Academy of Sciences 320 Yue-Yang Road, Shanghai 200031, China
*To whom correspondence should be addressed. Tel: 86 21 54921619; Fax: 86 21 54921116; Email: jpding{at}sibs.ac.cn
*Correspondence may also be addressed to Youxin Jin. Tel: 86 21 54921222; Fax: 86 21 54921011; Email: yxjin{at}sibs.ac.cn
Received May 8, 2006. Revised June 8, 2006. Accepted June 8, 2006.
Aminoacyl-tRNA synthetases (aaRSs) are a family of enzymes responsible for the covalent link of amino acids to their cognate tRNAs. The selectivity and species-specificity in the recognitions of both amino acid and tRNA by aaRSs play a vital role in maintaining the fidelity of protein synthesis. We report here the first crystal structure of human tryptophanyl-tRNA synthetase (hTrpRS) in complex with tRNATrp and Trp which, together with biochemical data, reveals the molecular basis of a novel tRNA binding and recognition mechanism. hTrpRS recognizes the tRNA acceptor arm from the major groove; however, the 3' end CCA of the tRNA makes a sharp turn to bind at the active site with a deformed conformation. The discriminator base A73 is specifically recognized by an 
-helix of the unique N-terminal domain and the anticodon loop by an -helix insertion of the C-terminal domain. The N-terminal domain appears to be involved in Trp activation, but not essential for tRNA binding and acylation. Structural and sequence comparisons suggest that this novel tRNA binding and recognition mechanism is very likely shared by other archaeal and eukaryotic TrpRSs, but not by bacterial TrpRSs. Our findings provide insights into the molecular basis of tRNA specificity and species-specificity.
The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors
Protein Data Bank accession codes 2AKE and 2DR2
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