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

Abstract

Significance Translation requires aminoacyl-tRNAs that are mainly formed by acylating tRNAs with the corresponding amino acids. Methanogenic archaea synthesize Cys-tRNA in an unusual indirect fashion. They attach a precursor amino acid, phosphoserine, to tRNA Cys , which is then converted to cysteine. This study shows that the indirect Cys-tRNA formation is carried out in a multienzyme complex assembled by a translation factor. Complex formation markedly promotes reaction efficiency. Because the indirect Cys-tRNA formation is the ancestral pathway of Cys biosynthesis in archaea, this complex may represent a remnant of a primordial machinery for Cys coding.

Structure of the Pseudomonas aeruginosa transamidosome reveals unique aspects of bacterial tRNA-dependent asparagine biosynthesis

“…Cys ) is essential for Cys-tRNA formation in methanogens (38). It is likely that the tRNA-dependent selenocysteine pathway also may involve a complex of tRNA Sec , SerRS, PSTK, and SepSecS (39).…”

Why Selenocysteine Is Unique?

“…The initial Ser residue present in the Ser-tRNA [Ser]Sec is phosphorylated by PSTK, resulting in an intermediate ophosposeryl-(Sep)-tRNA [Sep]Sec . Following the conversion, the o-phosphoseryl-tRNA Sec selenium transferase (SepSecS-a PLPdependent enzyme) performs the Sep/Sec conversion, resulting in the mature Sec-tRNA Sec (Liu et al, 2014). The biological selenium compound is delivered as mentioned for bacteria.…”

Structural basis for tRNA-dependent cysteine biosynthesis

“…This system also acts as the sole route for cysteine biosynthesis for these organisms 8 . More recently, it was reported that a third protein SepCysE (SepRS/SepCysS pathway enhancer) is necessary for coupling the consecutive two reactions and for enhancing tRNA Cys binding 11 . Thus, the SepRS, SepCysE, and SepCysS ternary complex (named the transsulfursome) is responsible for the whole process.…”

“…Thus, the SepRS, SepCysE, and SepCysS ternary complex (named the transsulfursome) is responsible for the whole process. SepCysE is preserved in class I methanogens, which evolved before other methanogens and may have appeared as the ancestral Euryarchaeota 11 , 12 . Therefore, elucidation of the functional mechanism of this system is of vital importance as it may explain the mechanism by which cysteine was added to the genetic code.…”

“…SepCysS is a homodimer with pyridoxal-5′-phosphate (PLP) bound in the active sites that shares structural similarity to the PLP-dependent cysteine desulfurase 10 , 15 . The structural analysis of SepCysS in complex with the N-terminal domain of SepCysE (SepCysE(NTD)) showed that the dimer of SepCysE is bound to the dimer of SepCysS with their dimer axes aligned 11 . However, it is not yet known how SepRS is bound to this binary complex to form a ternary complex (transsulfursome) and how Sep-tRNA Cys is transferred between these two enzymes safely.…”