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


ABSTRACT: 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-tRNA(Cys) (Sep-tRNA(Cys)), which is converted to Cys-tRNA(Cys) 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 tRNA(Cys) causing a 14-fold increase in the initial rate of Cys-tRNA(Cys) formation. Based on our crystal structure (2.8-Å resolution) of a SepCysS?SepCysE complex, a SepRS?SepCysE?SepCysS structure model suggests that this ternary complex enables substrate channeling of Sep-tRNA(Cys). 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.

SUBMITTER: Liu Y 

PROVIDER: S-EPMC4115501 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature

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

Liu Yuchen Y   Nakamura Akiyoshi A   Nakazawa Yuto Y   Asano Nozomi N   Ford Kara A KA   Hohn Michael J MJ   Tanaka Isao I   Yao Min M   Söll Dieter D  

Proceedings of the National Academy of Sciences of the United States of America 20140707 29


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-tRNA(Cys) (Sep-tRNA(Cys)), which is converted to Cys-tRNA(Cys) 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 Methan  ...[more]

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