A Model for Allosteric Communication in Drug Transport by the AcrAB-TolC Tripartite Efflux Pump
Abstract
:1. Introduction
2. Results
2.1. TolC Subunit Interface Contains Strongly Coupled Residue Pairs
2.2. ECs Correlate to Intrasubunit Movements in TolC and AcrA
2.3. TolC Periplasmic Helices Show Largest Outward Movement at the Quaternary Level
2.4. AcrA Domain Movements Corresponded to a Symmetrical Ring Contraction
2.5. An Increase in the Interface Surface Area Is Observed in the Transport State
2.6. Pattern of Interface Changes Is Conserved in Homologous Pump Assemblies
3. Discussion
3.1. ECs Maintain Tertiary Fold but Role at Subunit Interfaces Is Less Clear
3.2. Movement of TolC Periplasmic Helices and of AcrA BB Domain Appears to Be Evolutionary Conserved
3.3. AcrA and TolC Show a Quaternary, Symmetrical Switch on Pump Activation
3.4. Increase in Interface Area in Transport State Indicates a Favoured Energy State
3.5. AcrAB-TolC Conformational Changes Suggest an Allosteric Transport Model
3.6. The Allosteric Transport Model Might Be Common across Efflux Pumps
4. Materials and Methods
4.1. Evolutionary Couplings
4.2. Difference Distance Matrix
4.3. Interface Surface Area
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Webber, A.; Ratnaweera, M.; Harris, A.; Luisi, B.F.; Ntsogo Enguéné, V.Y. A Model for Allosteric Communication in Drug Transport by the AcrAB-TolC Tripartite Efflux Pump. Antibiotics 2022, 11, 52. https://doi.org/10.3390/antibiotics11010052
Webber A, Ratnaweera M, Harris A, Luisi BF, Ntsogo Enguéné VY. A Model for Allosteric Communication in Drug Transport by the AcrAB-TolC Tripartite Efflux Pump. Antibiotics. 2022; 11(1):52. https://doi.org/10.3390/antibiotics11010052
Chicago/Turabian StyleWebber, Anya, Malitha Ratnaweera, Andrzej Harris, Ben F. Luisi, and Véronique Yvette Ntsogo Enguéné. 2022. "A Model for Allosteric Communication in Drug Transport by the AcrAB-TolC Tripartite Efflux Pump" Antibiotics 11, no. 1: 52. https://doi.org/10.3390/antibiotics11010052