Structures of the interacting domains from yeast glutamyl-tRNA synthetase and tRNA-aminoacylation and nuclear-export cofactor Arc1p reveal a novel function for an old fold.
Eukaryotic aminoacyl-tRNA synthetases (aaRS) frequently contain additional appended domains that are absent from their prokaryotic counterparts which mediate complex formation between eukaryotic aaRS and cofactors of aminoacylation and translation. However, the structural basis of such interactions has remained elusive. The heteromerization domain of yeast glutamyl-tRNA synthetase (GluRS) has been cloned, expressed, purified and crystallized in space group C222(1), with unit-cell parameters a = 52, b = 107, c = 168 A. Phase information was obtained from multiple-wavelength anomalous dispersion with selenomethionine to 2.5 A resolution and the structure, comprising two monomers per asymmetric unit, was determined and refined to 1.9 A resolution. The structure of the interacting domain of its accessory protein Arc1p was determined and refined to 1.9 A resolution in a crystal form containing 20 monomers organized in five tetramers per asymmetric unit (space group C2, unit-cell parameters a = 222, b = 89, c = 127 A, beta = 99.4 degrees ). Both domains adopt a GST-like fold, demonstrating a novel role for this fold as a protein-protein interaction module.