Mutational separation of aminoacylation and cytokine activities of human tyrosyl-tRNA synthetase.
Mutational separation of aminoacylation and cytokine activities of human tyrosyl-tRNA synthetase.
复制标题
DOI：
10.1016/j.chembiol.2009.03.006
复制
发表时间：
2009-05-29
影响因子：
--
通讯作者：
Yang XL
中科院分区：
文献类型：
--
作者：
Kapoor M;Otero FJ;Slike BM;Ewalt KL;Yang XL
Aminoacyl-tRNA synthetases are known for catalysis of aminoacylation. Significantly, some mammalian synthetases developed cytokine functions possibly linked to disease-causing mutations in tRNA synthetases. Not understood is how epitopes for cytokine signaling were introduced into catalytic scaffolds without disturbing aminoacylation. Here we investigate human tyrosyl-tRNA synthetase, where a catalytic-domain surface helix—next to the active site—was recruited for IL-8-like cytokine signaling. Taking advantage of our high-resolution structure, the reciprocal impact of rational mutations designed to disrupt aminoacylation or cytokine signaling was investigated with multiple assays. The collective analysis demonstrated a protective fine–structure separation of aminoacylation from cytokine activities within the conserved catalytic domain. As a consequence, disease-causing mutations affecting cell signaling can arise without disturbing aminoacylation. These results with TyrRS also predict the previously unknown binding conformation of IL-8-like CXC cytokines.
登录
查看更多内容
影响因子：
4.8
作者：
Austin, J;First, EA
通讯作者：
First, EA
影响因子：
2.9
作者：
CALENDAR, R;BERG, P
通讯作者：
BERG, P
组酰基TRNA合成酶和天冬酰基-TRNA合成酶，肌炎中的自身抗原，激活T淋巴细胞上的趋化因子受体和未成熟的树突状细胞。
影响因子：
15.3
作者：
Howard, O M Zack;Dong, Hui Fang;Yang, De;Raben, Nina;Nagaraju, Kanneboyina;Rosen, Antony;Casciola-Rosen, Livia;Hartlein, Michael;Kron, Michael;Yang, David;Yiadom, Kwabena;Dwivedi, Sunita;Plotz, Paul H;Oppenheim, Joost J
通讯作者：
Oppenheim, Joost J
影响因子：
4.8
作者：
Ko, YG;Kim, EK;Kim, S
通讯作者：
Kim, S
影响因子：
4.8
作者：
Austin, J;First, EA
通讯作者：
First, EA