2azx

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2azx, resolution 2.8Å

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Charged and uncharged tRNAs adopt distinct conformations when complexed with human tryptophanyl-tRNA synthetase

Contents

Overview

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.

Disease

Known disease associated with this structure: Wolcott-Rallison syndrome OMIM:[604032]

About this Structure

2AZX is a Single protein structure of sequence from Homo sapiens with SO4, MG, TRP and GOL as ligands. Active as Tryptophan--tRNA ligase, with EC number 6.1.1.2 Full crystallographic information is available from OCA.

Reference

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

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