2. Academic Validation
  3. Structural insights of the elongation factor EF-Tu complexes in protein translation of Mycobacterium tuberculosis

Structural insights of the elongation factor EF-Tu complexes in protein translation of Mycobacterium tuberculosis

  • Commun Biol. 2022 Oct 3;5(1):1052. doi: 10.1038/s42003-022-04019-y.
Bowen Zhan 1,  Yanqing Gao 1,  Wenqing Gao 1,  Ye Li 1,  Zhengyang Li 1,  Qi Qi 1,  Xin Lan 1,  Hongbo Shen 2,  Jianhua Gan 1,  Guoping Zhao 3,  Jixi Li 4 5
Affiliations

Affiliations

  • 1 State Key Laboratory of Genetic Engineering, School of Life Sciences, Shanghai Engineering Research Center of Industrial Microorganisms, Fudan University, 200438, Shanghai, China.
  • 2 Shanghai Clinical Research Center for Infectious Disease (tuberculosis), Shanghai Pulmonary Hospital, Tongji University School of Medicine, 200433, Shanghai, China.
  • 3 Key Laboratory of Synthetic Biology, CAS Center for Excellence in Molecular Plant Sciences, Shanghai Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, 200031, Shanghai, China. [email protected].
  • 4 State Key Laboratory of Genetic Engineering, School of Life Sciences, Shanghai Engineering Research Center of Industrial Microorganisms, Fudan University, 200438, Shanghai, China. [email protected].
  • 5 Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, 200040, Shanghai, China. [email protected].
PMID: 36192483 DOI: 10.1038/s42003-022-04019-y
Abstract

Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) is the second-deadliest infectious disease worldwide. Emerging evidence shows that the elongation factor EF-Tu could be an excellent target for treating Mtb Infection. Here, we report the crystal structures of Mtb EF-Tu•EF-Ts and EF-Tu•GDP complexes, showing the molecular basis of EF-Tu's representative recycling and inactive forms in protein translation. Mtb EF-Tu binds with EF-Ts at a 1:1 ratio in solution and crystal packing. Mutation and SAXS analysis show that EF-Ts residues Arg13, Asn82, and His149 are indispensable for the EF-Tu/EF-Ts complex formation. The GDP binding pocket of EF-Tu dramatically changes conformations upon binding with EF-Ts, sharing a similar GDP-exchange mechanism in E. coli and T. ther. Also, the FDA-approved drug Osimertinib inhibits the growth of M. smegmatis, H37Ra, and M. bovis BCG strains by directly binding with EF-Tu. Thus, our work reveals the structural basis of Mtb EF-Tu in polypeptide synthesis and may provide a promising candidate for TB treatment.

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