Interplay between an ATP-binding cassette F protein and the ribosome from Mycobacterium tuberculosis

Authors

Zhicheng Cui, Texas A&M University
Xiaojun Li, Texas A&M University
Joonyoung Shin, Texas A&M University
Howard Gamper, Thomas Jefferson UniversityFollow
Ya-Ming Hou, Thomas Jefferson UniversityFollow
James C Sacchettini, Texas A&M University
Junjie Zhang, Texas A&M University

Document Type

Article

Publication Date

1-21-2022

Comments

This article is the author’s final published version in Nature Communications, Volume 13, Issue 1, January 2022, Article number 432.

The published version is available at https://doi.org/10.1038/s41467-022-28078-1. Copyright © Cui et al.

Abstract

EttA, energy-dependent translational throttle A, is a ribosomal factor that gates ribosome entry into the translation elongation cycle. A detailed understanding of its mechanism of action is limited due to the lack of high-resolution structures along its ATPase cycle. Here we present the cryo-electron microscopy (cryo-EM) structures of EttA from Mycobacterium tuberculosis (Mtb), referred to as MtbEttA, in complex with the Mtb 70S ribosome initiation complex (70SIC) at the pre-hydrolysis (ADPNP) and transition (ADP-VO4) states, and the crystal structure of MtbEttA alone in the post-hydrolysis (ADP) state. We observe that MtbEttA binds the E-site of the Mtb 70SIC, remodeling the P-site tRNA and the ribosomal intersubunit bridge B7a during the ribosomal ratcheting. In return, the rotation of the 30S causes conformational changes in MtbEttA, forcing the two nucleotide-binding sites (NBSs) to alternate to engage each ADPNP in the pre-hydrolysis states, followed by complete engagements of both ADP-VO4 molecules in the ATP-hydrolysis transition states. In the post-hydrolysis state, the conserved ATP-hydrolysis motifs of MtbEttA dissociate from both ADP molecules, leaving two nucleotide-binding domains (NBDs) in an open conformation. These structures reveal a dynamic interplay between MtbEttA and the Mtb ribosome, providing insights into the mechanism of translational regulation by EttA-like proteins.

Recommended Citation

Cui, Zhicheng; Li, Xiaojun; Shin, Joonyoung; Gamper, Howard; Hou, Ya-Ming; Sacchettini, James C; and Zhang, Junjie, "Interplay between an ATP-binding cassette F protein and the ribosome from Mycobacterium tuberculosis" (2022). Department of Biochemistry and Molecular Biology Faculty Papers. Paper 207.
https://jdc.jefferson.edu/bmpfp/207

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 License.

PubMed ID

35064151

Language

English