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Published February 16, 2016 | public
Journal Article

A Biophysical Approach Towards Understanding the Transport Mechanism of an ABC L-Methionine Importer

Li, Qi W.

Abstract

ABC transporters are prevalent in many kingdoms of life. In E. coli, one third of the transporters are ABC transporters. Their proper functions are vital to cell survival. Multiple drug resistance (MDR) transporters are a type of ABC transporters. They pump the drug out of the cell before the drug can exert its effects. Multidrug resistance is a major challenge in cancer and infectious diseases. Such resistance interferes with treatments and leads to longer recovery times and higher mortality rates. In addition, ABC transporters are important in chloride conductance, cholesterol transport, and surface-antigen presentation. ABC transporters in general also play a role in the regulation of movements of small molecules, ions, and macromolecules across membranes. MetNI was discovered by Kadner in the 1970s to efficiently uptake L-methionine in E. coli. In the MetNI system, the interplay between transporter and its binding protein, MetQ delivers L-methionine to the cell. Using a biophysical method, SPR, the kinetics of MetQ binding MetNI have been characterized and rate constants are extrapolated. Using a thermophoresis technique, MST, dissociation constants of this protein-protein interaction with different mutations, substrates, and nucleotide have been quantified. A transport mechanism, which consists of rate and equilibrium constants is being developed. By synthesizing the knowledge on the ATP hydrolysis, binding, transport, and conformational change, we will gain a better understanding of mechanisms of this intricate and important process. Importantly, this model will be able to help predict activities and stability of other members of the type I ABC transporters.

Additional Information

© 2016 Biophysical Society. Published by Elsevier Inc.

Additional details

Created:
August 20, 2023
Modified:
October 18, 2023