Structural basis for tRNA-dependent cysteine biosynthesis

Meirong Chen, Koji Kato, Yume Kubo, Yoshikazu Tanaka, Yuchen Liu, Feng Long, William B. Whitman, Pascal Lill, Christos Gatsogiannis, Stefan Raunser, Nobutaka Shimizu, Akira Shinoda, Akiyoshi Nakamura, Isao Tanaka, Min Yao

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Cysteine can be synthesized by tRNA-dependent mechanism using a two-step indirect pathway, where O-phosphoseryl-tRNA synthetase (SepRS) catalyzes the ligation of a mismatching O-phosphoserine (Sep) to tRNACys followed by the conversion of tRNA-bounded Sep into cysteine by Sep-tRNA:Cys-tRNA synthase (SepCysS). In ancestral methanogens, a third protein SepCysE forms a bridge between the two enzymes to create a ternary complex named the transsulfursome. By combination of X-ray crystallography, SAXS and EM, together with biochemical evidences, here we show that the three domains of SepCysE each bind SepRS, SepCysS, and tRNACys, respectively, which mediates the dynamic architecture of the transsulfursome and thus enables a global long-range channeling of tRNACys between SepRS and SepCysS distant active sites. This channeling mechanism could facilitate the consecutive reactions of the two-step indirect pathway of Cys-tRNACys synthesis (tRNA-dependent cysteine biosynthesis) to prevent challenge of translational fidelity, and may reflect the mechanism that cysteine was originally added into genetic code.

Original languageEnglish
Article number1521
JournalNature communications
Volume8
Issue number1
DOIs
Publication statusPublished - Dec 1 2017
Externally publishedYes

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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  • Cite this

    Chen, M., Kato, K., Kubo, Y., Tanaka, Y., Liu, Y., Long, F., Whitman, W. B., Lill, P., Gatsogiannis, C., Raunser, S., Shimizu, N., Shinoda, A., Nakamura, A., Tanaka, I., & Yao, M. (2017). Structural basis for tRNA-dependent cysteine biosynthesis. Nature communications, 8(1), [1521]. https://doi.org/10.1038/s41467-017-01543-y