Bonnefond Luc, Frugier Magali, Touzé Elodie, Lorber Bernard, Florentz Catherine, Giegé Richard, Sauter Claude, Rudinger-Thirion Joëlle
Département Machineries Traductionnelles, Architecture et Réactivité de l'ARN, Université Louis Pasteur de Strasbourg, CNRS, IBMC, 15 rue René Descartes, 67084 Strasbourg, France.
Structure. 2007 Nov;15(11):1505-16. doi: 10.1016/j.str.2007.09.018.
We report the structure of a strictly mitochondrial human synthetase, namely tyrosyl-tRNA synthetase (mt-TyrRS), in complex with an adenylate analog at 2.2 A resolution. The structure is that of an active enzyme deprived of the C-terminal S4-like domain and resembles eubacterial TyrRSs with a canonical tyrosine-binding pocket and adenylate-binding residues typical of class I synthetases. Two bulges at the enzyme surface, not seen in eubacterial TyrRSs, correspond to conserved sequences in mt-TyrRSs. The synthetase electrostatic surface potential differs from that of other TyrRSs, including the human cytoplasmic homolog and the mitochondrial one from Neurospora crassa. The homodimeric human mt-TyrRS shows an asymmetry propagating from the dimer interface toward the two catalytic sites and extremities of each subunit. Mutagenesis of the catalytic domain reveals functional importance of Ser200 in line with an involvement of A73 rather than N1-N72 in tyrosine identity.
我们报道了一种严格定位于线粒体的人类合成酶，即酪氨酰 - tRNA合成酶（mt - TyrRS）与一种腺苷酸类似物复合物的结构，分辨率为2.2埃。该结构是一种缺失C末端S4样结构域的活性酶，类似于真细菌TyrRS，具有典型的酪氨酸结合口袋和I类合成酶特有的腺苷酸结合残基。酶表面的两个凸起在真细菌TyrRS中未观察到，对应于mt - TyrRS中的保守序列。该合成酶的静电表面电势与其他TyrRS不同，包括人类细胞质同源物和粗糙脉孢菌的线粒体同源物。同型二聚体人类mt - TyrRS显示出一种从二聚体界面向每个亚基的两个催化位点和末端传播的不对称性。催化结构域的诱变揭示了Ser200的功能重要性，这与A73而非N1 - N72参与酪氨酸识别一致。
