Publication Abstract from PubMed
Human tryptophanyl-tRNA synthetase (TrpRS) is secreted into the extracellular region of vascular endothelial cells. 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 a resolution of 2.3 A and compared the structure with those of prokaryotic TrpRS and human mini TyrRS. Deletion of the tRNA anticodon-binding (TAB) domain insertion, consisting of eight residues in the human TrpRS, abolished the enzyme's apoptotic activity for endothelial cells, whereas its translational catalysis and cell-binding activities remained unchanged. Thus, we have identified the inserted peptide motif that activates the angiostatic signaling.
A short peptide insertion crucial for angiostatic activity of human tryptophanyl-tRNA synthetase.,Kise Y, Lee SW, Park SG, Fukai S, Sengoku T, Ishii R, Yokoyama S, Kim S, Nureki O Nat Struct Mol Biol. 2004 Feb;11(2):149-56. Epub 2004 Jan 11. PMID:14730354[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
