Structural Insights of the Elongation Factor EF-Tu Complexes in Protein Translation of Mycobacterium Tuberculosis

Overview

Journal Commun Biol

Specialty Biology

Date 2022 Oct 3

PMID 36192483

Authors

Bowen Zhan

Yanqing Gao

Wenqing Gao

Ye Li

Zhengyang Li

Qi Qi

Xin Lan

Hongbo Shen

Jianhua Gan

Guoping Zhao

Jixi Li

Affiliations

Soon will be listed here.

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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