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首页> 外文期刊>Molecular and Cellular Biology >Characterization of Human GTPBP3, a GTP-Binding Protein Involved in Mitochondrial tRNA Modification
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Characterization of Human GTPBP3, a GTP-Binding Protein Involved in Mitochondrial tRNA Modification

机译：人GTPBP3，涉及线粒体tRNA修饰的GTP结合蛋白的表征。

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Human GTPBP3 is an evolutionarily conserved, multidomain protein involved in mitochondrial tRNA modification. Characterization of its biochemical properties and the phenotype conferred by GTPBP3 inactivation is crucial to understanding the role of this protein in tRNA maturation and its effects on mitochondrial respiration. We show that the two most abundant GTPBP3 isoforms exhibit moderate affinity for guanine nucleotides like their bacterial homologue, MnmE, although they hydrolyze GTP at a 100-fold lower rate. This suggests that regulation of the GTPase activity, essential for the tRNA modification function of MnmE, is different in GTPBP3. In fact, potassium-induced dimerization of the G domain leads to stimulation of the GTPase activity in MnmE but not in GTPBP3. The GTPBP3 N-terminal domain mediates a potassium-independent dimerization, which appears as an evolutionarily conserved property of the protein family, probably related to the construction of the binding site for the one-carbon-unit donor in the modification reaction. Partial inactivation of GTPBP3 by small interfering RNA reduces oxygen consumption, ATP production, and mitochondrial protein synthesis, while the degradation of these proteins slightly increases. It also results in mitochondria with defective membrane potential and increased superoxide levels. These phenotypic traits suggest that GTPBP3 defects contribute to the pathogenesis of some oxidative phosphorylation diseases.
机译：人GTPBP3是一种进化保守的多域蛋白，参与线粒体tRNA修饰。表征其生化特性和GTPBP3失活赋予的表型对于理解该蛋白在tRNA成熟中的作用及其对线粒体呼吸的影响至关重要。我们显示，两个最丰富的GTPBP3亚型对鸟嘌呤核苷酸表现出中等亲和力，就像它们的细菌同源物MnmE一样，尽管它们水解GTP的速率降低了100倍。这表明，GTPBP3中对MnmE的tRNA修饰功能至关重要的GTPase活性调节不同。实际上，钾诱导的G结构域的二聚化会刺激MnmE中的GTPase活性，而不会刺激GTPBP3。 GTPBP3 N末端域介导了钾非依赖性二聚化，这表现为蛋白质家族的进化保守特性，可能与修饰反应中一个碳单位供体的结合位点的构建有关。小干扰RNA使 GTPBP3 部分失活可减少耗氧量，ATP生成和线粒体蛋白质合成，而这些蛋白质的降解略有增加。这也会导致线粒体的膜电位降低，超氧化物水平升高。这些表型性状表明GTPBP3缺陷有助于某些氧化磷酸化疾病的发病机理。

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