Abstract
Human tryptophanyl-tRNA synthetase (TrpRS) is secreted into the extracellular region of vascular endothelial cell. The splice variant form (mini TrpRS) functions in vascular endothelial cell apoptosis as an angiostatic cytokine. In contrast, the closely-related human tyrosyl-tRNA synthetase (TyrRS) functions as an angiogenic cytokine in its truncated form (mini TyrRS). Here, we determined the crystal structure of human mini TrpRS at 2.3 Å resolution, and compared the structure with those of prokaryotic TrpRS and human mini TyrRS. Among the three unique structural features of human TrpRS, deletion analyses revealed that only removal of the tRNA-anticodon-binding domain insertion, consisting of 8 residues, abolished the apoptotic activity for endothelial cells, while the translational catalytic activity and cell-binding activity remained unchanged. Thus, this work identified the inserted peptide motif important to activate the angiostatic signaling.
