Domain collapse and active site ablation generate a widespread animal mitochondrial seryl-tRNA synthetase.

Through their aminoacylation reactions, aminoacyl tRNA-synthetases (aaRS) establish the rules of the genetic code throughout all of nature. During their long evolution in eukaryotes, additional domains and splice variants were added to what is commonly a homodimeric or monomeric structure. These changes confer orthogonal functions in cellular activities that have recently been uncovered. An unusual exception to the familiar architecture of aaRSs is the heterodimeric metazoan mitochondrial SerRS. In contrast to domain additions or alternative splicing, here we show that heterodimeric metazoan mitochondrial SerRS arose from its homodimeric ancestor not by domain additions, but rather by collapse of an entire domain (in one subunit) and an active site ablation (in the other). The collapse/ablation retains aminoacylation activity while creating a new surface, which is necessary for its orthogonal function. The results highlight a new paradigm for repurposing a member of the ancient tRNA synthetase family.

氨酰-tRNA合成酶（aaRS）通过其氨酰化反应，在整个自然界中确立了遗传密码的规则。在真核生物的长期进化过程中，在通常为同二聚体或单体的结构上添加了额外的结构域和剪接变体。这些变化赋予了最近才被发现的细胞活动中的正交功能。aaRS常见结构的一个不寻常的例外是后生动物线粒体异二聚体丝氨酸-tRNA合成酶（SerRS）。与结构域添加或可变剪接不同，我们在此表明，后生动物线粒体异二聚体SerRS由其同二聚体祖先产生，不是通过结构域添加，而是通过一个完整结构域（在一个亚基中）的缺失和一个活性位点的消除（在另一个亚基中）。这种缺失/消除保留了氨酰化活性，同时产生了一个新的表面，这对其正交功能是必需的。这些结果凸显了重新利用古老的tRNA合成酶家族成员的一种新模式。