Leucyl-tRNA synthetases (LeuRS) catalyze the attachment of leucine to tRNALeu and play fundamental role in protein synthesis. According to evolutionary models, the primitive catalytic core of LeuRS was extended by the insertion and appendage of additional domains (also called modules). Most LeuRSs carry a large insert called the connective polypeptide 1 (CP1) domain that is responsible for the amino acid-editing function. LeuRSs also exhibit tRNA-binding domains and C-terminal domains that recognize and bind tRNALeu isoacceptors and a well-ordered module inserted into the catalytic domain leucine-specific domain (LSD). Besides, a highly conserved structural module following the KMSKS loop exhibits the characteristic α-α-β-α topology in most class Ia and Ib aaRSs, which was named SC-fold. However, the function of this domain was rarely reported.
Recently, Dr. YAN Wei and her colleagues under the guidance of Professor WANG Enduo from the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, CAS, systematically investigated the key residues of the conserved SC-fold structural module in prokaryotic and eukaryotic LeuRSs. Crucial basic and Gly residues in the third α-helix (α3) of the SC-fold were found to modulate the aminoacylation and editing activities of LeuRS. Additionally, several key residues of helix 3 interact with the tRNALeu anticodon stem, whereas acidic residues of the β-strand control the tRNA-dependent editing activity by sensing the size of the tRNALeu D-loop. These findings were further confirmed by experiments performed on the chimeric MmLeuRS-CP1/LSD enzyme, a minimalist LeuRS enzyme fused with E. coli CP1 domain and LSD . The role of the β-strand in enhancing the editing activity of the chimera was further confirmed by substituting the crucial residues for the E. coli enzyme. Together, these results support an influential role for the SC-fold module in both aminoacylation and editing functions of LeuRSs. The results suggested that except synthetic and editing domains of LeuRS, SCF might be a new target of antibiotic against pathogen.
This work entitled “Modulation of aminoacylation and editing properties of leucyl-tRNA synthetase by a conserved structural module” was published online in The Journal of Biological Chemistry on Mar 27 It was funded by the Natural Science Foundation of China, the National Key Basic Research Foundation of China, the Chinese Academy of Sciences, and the Committee of Science and Technology in Shanghai.
AUTHOR CONTACT:
WANG Enduo
Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences
Shanghai 200031, China.
Phone: 86-21-54921241;
E-mail: edwang@sibcb.ac.cn
Fig. Tertiary structure of E. coli LeuRS and the crucial amino acid residues of SCF.
(Image provided by Prof. WANG Enduo’s group)
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