Charged and uncharged tRNAs adopt distinct conformations when complexed with human tryptophanyl-tRNA synthetase
[SYWC_HUMAN] Isoform 1, isoform 2 and T1-TrpRS have aminoacylation activity while T2-TrpRS lacks it. Isoform 2, T1-TrpRS and T2-TrpRS possess angiostatic activity whereas isoform 1 lacks it. T2-TrpRS inhibits fluid shear stress-activated responses of endothelial cells. Regulates ERK, Akt, and eNOS activation pathways that are associated with angiogenesis, cytoskeletal reorganization and shear stress-responsive gene expression.   
Publication Abstract from PubMed
Aminoacylation of tRNA is the first step of protein synthesis. Here, we report the co-crystal structure of human tryptophanyl-tRNA synthetase and tRNATrp. This enzyme is reported to interact directly with elongation factor 1alpha, which carries charged tRNA to the ribosome. Crystals were generated from a 50/50% mixture of charged and uncharged tRNATrp. These crystals captured two conformations of the complex, which are nearly identical with respect to the protein and a bound tryptophan. They are distinguished by the way tRNA is bound. In one, uncharged tRNA is bound across the dimer, with anticodon and acceptor stem interacting with separate subunits. In this cross-dimer tRNA complex, the class I enzyme has a class II-like tRNA binding mode. This structure accounts for biochemical investigations of human TrpRS, including species-specific charging. In the other conformation, presumptive aminoacylated tRNA is bound only by the anticodon, the acceptor stem being free and having space to interact precisely with EF-1alpha, suggesting that the product of aminoacylation can be directly handed off to EF-1alpha for the next step of protein synthesis.
Two conformations of a crystalline human tRNA synthetase-tRNA complex: implications for protein synthesis.,Yang XL, Otero FJ, Ewalt KL, Liu J, Swairjo MA, Kohrer C, RajBhandary UL, Skene RJ, McRee DE, Schimmel P EMBO J. 2006 Jun 21;25(12):2919-29. Epub 2006 May 25. PMID:16724112
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.