7MU0

MtbEttA in the ADP bound state

Summary for 7MU0

• Entry DOI: 10.2210/pdb7mu0/pdb
• Related: 7MSC 7MSH 7MSM 7MSZ
• Descriptor: Energy-dependent translational throttle protein EttA, ADENOSINE-5'-DIPHOSPHATE, MAGNESIUM ION (3 entities in total)
• Functional Keywords: mycobacterium tuberculosis, ribosome, abcf ribosome complex, antibiotic, hydrolase
• Biological source: Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv)
• Total number of polymer chains: 2
• Total formula weight: 125751.94

Authors

Cui, Z.,Zhang, J. (deposition date: 2021-05-14, release date: 2022-02-02, Last modification date: 2023-10-18)

Primary citation

Cui, Z.,Li, X.,Shin, J.,Gamper, H.,Hou, Y.M.,Sacchettini, J.C.,Zhang, J.
Interplay between an ATP-binding cassette F protein and the ribosome from Mycobacterium tuberculosis.
Nat Commun, 13:432-432, 2022

PubMed 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-VO) 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-VO 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.

PubMed: 35064151
DOI: 10.1038/s41467-022-28078-1

Experimental method

X-RAY DIFFRACTION (2.9 Å)