A short peptide insertion crucial for angiostatic activity of human tryptophanyl-tRNA synthetase
A short peptide insertion crucial for angiostatic activity of human tryptophanyl-tRNA synthetase
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DOI：
10.1038/nsmb722
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发表时间：
2004-02-01
影响因子：
16.8
通讯作者：
Nureki, O
中科院分区：
文献类型：
--
作者：
Kise, Y;Lee, SW;Nureki, O
人尿苷酰-tRNA合成酶（TrpRS）分泌到血管内皮细胞的细胞外区域。剪接变体形式（miniTrpRS）作为血管生成抑制性细胞因子在血管内皮细胞凋亡中起作用。相反，密切相关的人酪氨酰-tRNA合成酶（TyrRS）以其截短形式（迷你TyrRS）作为血管生成细胞因子起作用。在此，我们以2.3埃的分辨率确定了人mini TrpRS的晶体结构，并将其结构与原核TrpRS和人mini TyrRS的结构进行了比较。删除的tRNA anticodon-binding（TAB）结构域插入，在人类TrpRS的8个残基组成，废除了酶的内皮细胞的凋亡活性，而其翻译催化和细胞结合活性保持不变。因此，我们已经确定了插入的肽基序，激活血管生成抑制信号。
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 Angstrom 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.