7KGG

Cryo-EM Structures of AdeB from Acinetobacter baumannii: AdeB-ET-I

Summary for 7KGG

• Entry DOI: 10.2210/pdb7kgg/pdb
• EMDB information: 22869
• Descriptor: Efflux pump membrane transporter, PHOSPHATIDYLETHANOLAMINE, ETHIDIUM (3 entities in total)
• Functional Keywords: adeb, acinetobacter baumannii, membrane protein, cryo-em, rnd transporter, transport protein
• Biological source: Acinetobacter baumannii
• Total number of polymer chains: 3
• Total formula weight: 343112.34

Authors

Morgan, C.E.,Yu, E.W. (deposition date: 2020-10-16, release date: 2021-03-10, Last modification date: 2024-03-06)

Primary citation

Morgan, C.E.,Glaza, P.,Leus, I.V.,Trinh, A.,Su, C.C.,Cui, M.,Zgurskaya, H.I.,Yu, E.W.
Cryoelectron Microscopy Structures of AdeB Illuminate Mechanisms of Simultaneous Binding and Exporting of Substrates.
Mbio, 12:-, 2021

PubMed Abstract: is a Gram-negative pathogen that has emerged as one of the most highly antibiotic-resistant bacteria worldwide. Multidrug efflux within these highly drug-resistant strains and other opportunistic pathogens is a major cause of failure of drug-based treatments of infectious diseases. The best-characterized multidrug efflux system in is the prevalent rug fflux B (AdeB) pump, which is a member of the resistance-nodulation-cell division (RND) superfamily. Here, we report six structures of the trimeric AdeB multidrug efflux pump in the presence of ethidium bromide using single-particle cryoelectron microscopy (cryo-EM). These structures allow us to directly observe various novel conformational states of the AdeB trimer, including the transmembrane region of trimeric AdeB can be associated with form a trimer assembly or dissociated into "dimer plus monomer" and "monomer plus monomer plus monomer" configurations. We also discover that a single AdeB protomer can simultaneously anchor a number of ethidium ligands and that different AdeB protomers can bind ethidium molecules simultaneously. Combined with molecular dynamics (MD) simulations, we reveal a drug transport mechanism that involves multiple multidrug-binding sites and various transient states of the AdeB membrane protein. Our data suggest that each AdeB protomer within the trimer binds and exports drugs independently. has emerged as one of the most highly antibiotic-resistant Gram-negative pathogens. The prevalent AdeB multidrug efflux pump mediates resistance to a broad spectrum of clinically relevant antimicrobial agents. Here, we report six cryo-EM structures of the trimeric AdeB pump in the presence of ethidium bromide. We discover that a single AdeB protomer can simultaneously anchor a number of ligands, and different AdeB protomers can bind ethidium molecules simultaneously. The results indicate that each AdeB protomer within the trimer recognizes and extrudes drugs independently.

PubMed: 33622726
DOI: 10.1128/mBio.03690-20

Experimental method

ELECTRON MICROSCOPY (2.97 Å)