Ancient translation factor is essential for tRNA-dependent cysteine biosynthesis in methanogenic archaea

作者：Liu Yuchen; Nakamura Akiyoshi; Nakazawa Yuto; Asano Nozomi; Ford Kara A; Hohn Michael J; Tanaka Isao; Yao Min^*; Soell Dieter

来源：Proceedings of the National Academy of Sciences of the United States of America, 2014, 111(29): 10520-10525.

DOI：10.1073/pnas.1411267111

• methanogen
• aminoacyl-tRNA
• protein complex

Methanogenic archaea lack cysteinyl-tRNA synthetase; they synthesize Cys-tRNA and cysteine in a tRNA-dependent manner. Two enzymes are required: Phosphoseryl-tRNA synthetase (SepRS) forms phosphoseryl-tRNACys (Sep-tRNACys), which is converted to Cys-tRNACys by Sep-tRNA: Cys-tRNA synthase (SepCysS). This represents the ancestral pathway of Cys biosynthesis and coding in archaea. Here we report a translation factor, SepCysE, essential for methanococcal Cys biosynthesis; its deletion in Methanococcus maripaludis causes Cys auxotrophy. SepCysE acts as a scaffold for SepRS and SepCysS to form a stable high-affinity complex for tRNACys causing a 14-fold increase in the initial rate of Cys-tRNACys formation. Based on our crystal structure (2.8-angstrom resolution) of a SepCysS SepCysE complex, a SepRS SepCysE SepCysS structure model suggests that this ternary complex enables substrate channeling of Sep-tRNACys. A phylogenetic analysis suggests coevolution of SepCysE with SepRS and SepCysS in the last universal common ancestral state. Our findings suggest that the tRNA-dependent Cys biosynthesis proceeds in a multienzyme complex without release of the intermediate and this mechanism may have facilitated the addition of Cys to the genetic code.

• 出版日期2014-7-22