The DRS-AIMP2-EPRS subcomplex acts as a pivot in the multi-tRNA synthetase complex

Area of Science:

• Biochemistry
• Structural Biology
• Molecular Biology

Background:

• Aminoacyl-tRNA synthetases (ARSs) are crucial for protein biosynthesis and other cellular functions.
• Nine ARSs and three scaffold proteins (AIMPs) form the multi-tRNA synthetase complex (MSC) for cooperativity.
• Understanding MSC assembly is vital for comprehending its cellular roles.

Purpose of the Study:

• To determine the structure of a specific ternary subcomplex within the MSC.
• To elucidate the interaction mechanisms between aspartyl-tRNA synthetase (DRS) and glutathione S-transferase (GST) domains of AIMP2 and EPRS.
• To gain insights into the overall assembly and disassembly of the MSC.

Main Methods:

• X-ray crystallography was employed to determine the structure of the DRS-AIMP2_GST-EPRS_GST ternary subcomplex.
• Analysis of protein-protein interactions within the subcomplex.

Main Results:

• AIMP2_GST and EPRS_GST interact through conventional GST heterodimerization.
• DRS interacts strongly with AIMP2_GST via specific hydrogen bonds involving the α7-β9 loop of DRS and the β2-α2 loop of AIMP2_GST.
• Serine 156 of AIMP2_GST was identified as essential for the assembly of this subcomplex.

Conclusions:

• The determined structure provides critical insights into the architecture of the MSC.
• The findings illuminate the molecular basis for MSC assembly and potential disassembly mechanisms.
• This structural information is valuable for understanding the functional dynamics of the MSC.