Related Experiment Video
Updated: May 29, 2026

Native Cell Membrane Nanoparticles System for Membrane Protein-Protein Interaction Analysis
Published on: July 16, 2020
Elastic network model-based normal mode analysis reveals the conformational couplings in the tripartite AcrAB-TolC
Beibei Wang1, Jingwei Weng, Kangnian Fan
1Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, Department of Chemistry and Institute of Biomedical Sciences, Fudan University, Shanghai, People's Republic of China.
Abstract:
The AcrAB-TolC drug efflux system, energized by proton movement down the transmembrane electrochemical gradient, is responsible for the resistance of the organism to a wide range of drugs. Experimental data suggest functional roles of each part of the assembly, but the detailed working mechanism of this machinery remains elusive. We used elastic network-based normal mode analysis (NMA) to explore the conformational dynamics of the AcrAB-TolC complex. The intrinsic flexibilities of the pore domain in AcrB monomer conform to the previously proposed three-step functionally rotating mechanism for asymmetric AcrB trimer. Conformational couplings across monomers in the AcrB trimer were observed, and the coupling between the transmembrane domain and the other parts of AcrB are strengthened through trimeric assembly. In the tripartite AcrAB-TolC assembly obtained through molecular docking, concerted motions were observed not only at the direct contact interfaces between various components but also between distant parts of the whole complex. The presence of AcrA was shown to significantly strengthen the motional couplings between AcrB and TolC. Overall, NMA revealed an allosteric network in the AcAB-TolC efflux system, which provides hints to our understanding of its detailed working mechanism.
Related Concept Videos
Membrane Asymmetry Regulating Transporters
Flippase
Eukaryotic flippases are type-IV P-type ATPases or P4-ATPases belonging to P-type ATPase family proteins that are membrane-bound pumps involved in the ATP-mediated transport of ions and molecules across the membrane. Flippases flip specific phospholipids from the outer to the inner leaflet of a membrane. All P4-ATPases have one...
Drug Absorption Mechanism: Passive Membrane Transport
Drug Absorption Mechanism: Carrier-Mediated Membrane Transport
Facilitated diffusion is a passive process that utilizes human Solute Carrier (SLC) transporters. These transporters bind to the drug, undergo structural...
Pharmacodynamic Models: Emax Drug–Concentration Effect Model
Pharmacodynamic Models: Linear Concentration–Effect Model
The Two-State Receptor Model
The binding affinity of a drug determines its interaction with one...
