Structural basis for tRNA-dependent cysteine biosynthesis.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 29142195.
- Also identified by DOI 10.1038/s41467-017-01543-y and PMC identifier 5688128.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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 tRNA<sup>Cys</sup> 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<sup>Cys</sup>, respectively, which mediates the dynamic architecture of the transsulfursome and thus enables a global long-range channeling of tRNA<sup>Cys</sup> between SepRS and SepCysS distant active sites. This channeling mechanism could facilitate the consecutive reactions of the two-step indirect pathway of Cys-tRNA<sup>Cys</sup> synthesis (tRNA-dependent cysteine biosynthesis) to prevent challenge of translational fidelity, and may reflect the mechanism that cysteine was originally added into genetic code.
Medical subject headings
- Amino Acyl-tRNA Synthetases
- Archaeal Proteins
- Cysteine
- RNA, Transfer, Cys