Structural basis for double-sieve discrimination of L-valine from L-isoleucine and L-threonine by the complex of tRNA(Val) and valyl-tRNA synthetase

Academic Article

Abstract

  • Valyl-tRNA synthetase (ValRS) strictly discriminates the cognate L-valine from the larger L-isoleucine and the isosteric L-threonine by the tRNA-dependent 'double sieve' mechanism. In this study, we determined the 2.9 Å crystal structure of a complex of Thermus thermophilus ValRS, tRNA(Val), and an analog of the Val-adenylate intermediate. The analog is bound in a pocket, where Pro41 allows accommodation of the Val and Thr moieties but precludes the lle moiety (the first sieve), on the aminoacylation domain. The editing domain, which hydrolyzes incorrectly synthesized Thr-tRNA(Val), is bound to the 3' adenosine of tRNA(Val). A contiguous pocket was found to accommodate the Thr moiety, but not the Val moiety (the second sieve). Furthermore, another Thr binding pocket for Thr-adenylate hydrolysis was suggested on the editing domain.
  • Published In

  • Cell  Journal
  • Digital Object Identifier (doi)

    Author List

  • Fukai S; Nureki O; Sekine SI; Shimada A; Tao J; Vassylyev DG; Yokoyama S
  • Start Page

  • 793
  • End Page

  • 803
  • Volume

  • 103
  • Issue

  • 5