Laboratoire d'Enzymologie et Biochimie Structurales, CNRS, 91190 Gif-sur-Yvette, France.
Protein Sci. 2010 Dec;19(12):2475-84. doi: 10.1002/pro.529.
Methionyl-tRNA synthetase (MetRS) is a multidomain protein that specifically binds tRNAMet and catalyzes the synthesis of methionyl-tRNAMet. The minimal, core enzyme found in Aquifex aeolicus is made of a catalytic domain, which catalyzes the aminoacylation reaction, and an anticodon-binding domain, which promotes tRNA-protein association. In eukaryotes, additional domains are appended in cis or in trans to the core enzyme and increase the stability of the tRNA-protein complexes. Eventually, as observed for MetRS from Homo sapiens, the C-terminal appended domain causes a slow release of aminoacyl-tRNA and establishes a limiting step in the global aminoacylation reaction. Here, we report that MetRS from the nematode Caenorhabditis elegans displays a new type of structural organization. Its very C-terminal appended domain is related to the oligonucleotide binding-fold-based tRNA-binding domain (tRBD) recovered at the C-terminus of MetRS from plant, but, in the nematode enzyme, this domain is separated from the core enzyme by an insertion domain. Gel retardation and tRNA aminoacylation experiments show that MetRS from nematode is functionally related to human MetRS despite the fact that their appended tRBDs have distinct structural folds, and are not orthologs. Thus, functional convergence of human and nematode MetRS is the result of parallel and convergent evolution that might have been triggered by the selective pressure to invent processivity of tRNA handling in translation in higher eukaryotes.
甲硫氨酰-tRNA 合成酶(MetRS)是一种具有多个结构域的蛋白质,它能特异性地结合 tRNAMet,并催化甲硫氨酰-tRNA 的合成。在水生栖热菌(Aquifex aeolicus)中发现的最小核心酶由催化结构域和反密码子结合结构域组成,前者催化氨酰化反应,后者促进 tRNA 与蛋白质的结合。在真核生物中,核心酶的顺式或反式附加结构域增加了 tRNA-蛋白质复合物的稳定性。最终,正如人类 MetRS 所观察到的,C 末端附加结构域导致氨酰-tRNA 的缓慢释放,并成为全局氨酰化反应的限速步骤。在这里,我们报告线虫 Caenorhabditis elegans 的 MetRS 显示出一种新的结构组织方式。其非常 C 末端的附加结构域与植物 MetRS 的 C 末端发现的寡核苷酸结合折叠 tRNA 结合结构域(tRBD)有关,但在该线虫酶中,这个结构域与核心酶通过插入结构域隔开。凝胶阻滞和 tRNA 氨酰化实验表明,尽管其附加的 tRBD 具有不同的结构折叠,且不是同源物,但线虫 MetRS 在功能上与人类 MetRS 相关。因此,人类和线虫 MetRS 的功能趋同是平行和趋同进化的结果,这种进化可能是由提高真核生物翻译中 tRNA 处理的持续性的选择压力引发的。