Structural basis for tRNA-dependent cysteine biosynthesis

• Published in: Nature communications Vol. 8; no. 1; pp. 1521 - 12
• Main Authors: Chen, Meirong, Kato, Koji, Kubo, Yume, Tanaka, Yoshikazu, Liu, Yuchen, Long, Feng, Whitman, William B., Lill, Pascal, Gatsogiannis, Christos, Raunser, Stefan, Shimizu, Nobutaka, Shinoda, Akira, Nakamura, Akiyoshi, Tanaka, Isao, Yao, Min
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 15.11.2017; Nature Publishing Group; Nature Portfolio
• Subjects: 631/337/574/1793; 631/45/535/1258; 631/45/535/1261; 631/45/535/1266; Biosynthesis; Channeling; Chemical synthesis; Crystallography; Cysteine; Genetic code; Humanities and Social Sciences; Methanogenic bacteria; multidisciplinary; Phosphoserine; Science; Science (multidisciplinary); Small angle X ray scattering; tRNA Cys; X-ray crystallography
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-017-01543-y

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 tRNA Cys 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 tRNA Cys , respectively, which mediates the dynamic architecture of the transsulfursome and thus enables a global long-range channeling of tRNA Cys between SepRS and SepCysS distant active sites. This channeling mechanism could facilitate the consecutive reactions of the two-step indirect pathway of Cys-tRNA Cys synthesis (tRNA-dependent cysteine biosynthesis) to prevent challenge of translational fidelity, and may reflect the mechanism that cysteine was originally added into genetic code. tRNA-dependent cysteine biosynthesis is catalyzed by the transsulfursome protein complex. Here, the authors use a multidisciplinary approach to structurally characterize the archaeal transsulfursome and propose a model for tRNA channeling in the complex.