Retractile lysyl-tRNA synthetase-AIMP2 assembly in the human multi-aminoacyl-tRNA synthetase complex

Hei, Zhoufei; Wu, Siqi; Liu, Zaizhou; Wang, Jing; Fang, Pengfei

doi:10.1074/jbc.RA118.006356

Title: Retractile lysyl-tRNA synthetase-AIMP2 assembly in the human multi-aminoacyl-tRNA synthetase complex

Journal Article · Thu Feb 07 00:00:00 EST 2019 · Journal of Biological Chemistry

DOI:https://doi.org/10.1074/jbc.RA118.006356· OSTI ID:1504973

^[1]; Wu, Siqi ^[1]; Liu, Zaizhou ^[1]; Wang, Jing ^[1];

^[1]

Chinese Academy of Sciences (CAS), Shanghai (China)

Multi-aminoacyl-tRNA synthetase complex (MSC) is the second largest machinery for protein synthesis in human cells and also regulates multiple nontranslational functions through its components. Prior studies have shown that the MSC can respond to external signals by releasing its components to function outside it. The internal assembly is fundamental to MSC regulation. Here, using crystal structural analyses (at 1.88 Å resolution) along with molecular modeling, gel-filtration chromatography, and co-immunoprecipitation, we report that human lysyl-tRNA synthetase (LysRS) forms a tighter assembly with the scaffold protein aminoacyl-tRNA synthetase complex-interacting multifunctional protein 2 (AIMP2) than previously observed. Wefound that two AIMP2 N-terminal peptides form an antiparallel scaffold and hold two LysRS dimers through four binding motifs and additional interactions. Of note, the four catalytic subunits of LysRS in the tightly assembled complex were all accessible for tRNA recognition. We further noted that two recently reported human disease-associated mutations conflict with this tighter assembly, cause LysRS release from the MSC, and inactivate the enzyme. These findings reveal a previously unknown dimension of MSC subcomplex assembly and suggest that the retractility of this complex may be critical for its physiological functions.

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Research Organization:: Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Organization:: National Natural Science Foundation of China (NSFC); Chinese Academy of Sciences (CAS); State Key Laboratory of Bioorganic and Natural Products Chemistry

Grant/Contract Number:: 21778064; XDB20000000; 21778067

OSTI ID:: 1504973

Journal Information:: Journal of Biological Chemistry, Vol. 294, Issue 13; ISSN 0021-9258

Publisher:: American Society for Biochemistry and Molecular BiologyCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

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Cited by: 13 works

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59 BASIC BIOLOGICAL SCIENCES
37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
aminoacyl tRNA synthetase
protein complex
crystal structure
molecular biology
translation
aminoacyl-tRNA syntheses complex-interacting multifunctional protein 2 (AIMP2)
cardiomyopathy
lysyl-tRNA synthetase (LysRS)
multi-aminoacyl-tRNA syntheses complex (MSC)

Title: Retractile lysyl-tRNA synthetase-AIMP2 assembly in the human multi-aminoacyl-tRNA synthetase complex

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