title: A short peptide insertion crucial for angiostatic activity of human tryptophanyl-tRNA synthetase.
abstract: 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.
authors.affiliation: Department of Biophysics and Biochemistry, Graduate School of Science, the University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Kise
authors.forename: Sang Won
authors.initials: SW
authors.lastname: Lee
authors.forename: Sang Gyu
authors.initials: SG
authors.lastname: Park
authors.forename: Shuya
authors.initials: S
authors.lastname: Fukai
authors.forename: Toru
authors.initials: T
authors.lastname: Sengoku
authors.forename: Ryohei
authors.initials: R
authors.lastname: Ishii
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Yokoyama
authors.forename: Sunghoon
authors.initials: S
authors.lastname: Kim
authors.forename: Osamu
authors.initials: O
authors.lastname: Nureki
mesh_terms: D017209:Apoptosis; D006801:Humans; D008958:Models, Molecular; D018919:Neovascularization, Physiologic; D010455:Peptides / Q000502:physiology*; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D014369:Tryptophan-tRNA Ligase / Q000737:chemistry / Q000502:physiology*
chemical_list: D010455:Peptides; D011994:Recombinant Proteins; D014369:Tryptophan-tRNA Ligase