In protein synthesis, aminoacyl-tRNA synthetase (AARS) catalyzes the ligation of amino acid with its cognate tRNAs to generate aminoacyl-tRNA for the ribosome. The correct pairing of an amino acid and tRNAs is of great importance for life. AARS needs to charge tRNAs with high accuracy to meet protein synthesis. However, some AARSs mis-activate non-cognate amino acids and thus produce mis-activated amino acids and mis-charged tRNAs. Thus, a proofreading (editing) activity is required in some AARSs to hydrolyze any errors, ensuring a high level of translational fidelity.
Threonyl-tRNA synthetase (ThrRS) belongs to class II AARS and contains N1 domain (with unknown function), N2 editing domain, aminoacylation domain and C-terminal tRNA binding domain. The potential function of N1 in aminoacylation and editing has not been clarified till now. Recently, Dr. ZHOU Xiaolong, Ph. D candidate CHEN Yun and their colleagues under the guidance of Professor WANG Enduo at the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, CAS found strikingdifferences in N1 domain composition and editing active sites in the N2 domain of various bacteria from Mycoplasma species, clarified the translational quality control mechanisms of various bacterial ThrRSs by in vitro and in vivo analyses, revealed the crucial importance of the N1 domain in regulating editing by mediating an N1-N2 domain interaction in Escherichia coli ThrRS. This study revealed the crucial importance of N1 domain in translational quality control. Interrupting the N1-N2 domain interaction would lead to mistranslation and then stop the growth of microorganisms.
This work is funded by the National Key Basic Research Foundation of China, the Natural Science Foundation of China, the Chinese Academy of Sciences (CAS), the Youth Innovation Promotion Association from CAS (to XLZ) and the Shanghai Rising-Star Program.
Figure: Crystal structure of the EcThrRS-tRNAThrcomplex (PDB 1QF6) showing the spatial location of the Asp46-containing N1 domain and the Tyr173 and His186-containing N2 domain.
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