9J3E

Cryo-EM structure of TMexCD1-TOprJ1 in complex with 1-(1-naphthylmethyl)piperazine

This is a non-PDB format compatible entry.

Summary for 9J3E

• Entry DOI: 10.2210/pdb9j3e/pdb
• EMDB information: 61115
• Descriptor: RND efflux system, OprJ-like protein, RND efflux system, MexC-like protein, Efflux pump membrane transporter, ... (4 entities in total)
• Functional Keywords: efflux pump, transporter, antibiotics, antimicrobial resistance, transport protein
• Biological source: Klebsiella pneumoniae; More
• Total number of polymer chains: 12
• Total formula weight: 750809.38

Authors

Shi, Y.,Feng, Y. (deposition date: 2024-08-08, release date: 2025-08-13, Last modification date: 2026-02-25)

Primary citation

Shi, Y.,Li, M.,Cui, T.,Gan, J.,Huang, H.,Su, Z.,Yang, R.,Zhang, X.,Zhang, H.,Feng, Y.,Feng, Y.
Assembly and inhibition of transferable TMexCD1-TOprJ1 efflux pump.
Nat Commun, 16:10025-10025, 2025

PubMed Abstract: Recent emergence and dissemination of plasmid-borne tmexCD1-toprJ1 tigecycline resistance threatens the efficacy of tigecycline as a "last-resort" defense against bacterial infections. Here, we report two cryo-EM structures of TMexCD1-TOprJ1 alone and in complex with its NMP inhibitor, and both are determined at the resolutions of 2.97 Å and 3.0 Å, respectively. The symmetry of overall architecture explains how the tripartite organization adopts a 3:6:3 protomer stoichiometry (TOprJ1: TMexC1: TMexD1) to assemble an elongated, rod-like pump spanning bacterial double membranes. The periplasmic TMexC1 adaptor bind the trimeric TOprJ1 funnel via a universal "tip-to-tip" contact, and bridges the bottom TMexD1 engine by extensive interactions. A unique form of resting (R) states is observed for TMexD1 trimer. Besides two binding-interfaces of TMexC1 with TOprJ1 and TMexD1, we characterize a substrate/inhibitor-loading cavity. Collectively, these findings constitute molecular bases for assembly and inhibition of transferable TMexCD1-TOprJ1 machinery, and benefit developing next-generation of antimicrobials targeting functional efflux pump.

PubMed: 41238543
DOI: 10.1038/s41467-025-65038-x

Experimental method

ELECTRON MICROSCOPY (3 Å)