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Expression, Detergent Solubilization, and Purification of a Membrane Transporter, the MexB Multidrug Resistance Protein
Published on: December 3, 2010
The choreography of multidrug export
Rupak Doshi1, Daniel A P Gutmann, Yvonne S K Khoo
1Department of Pharmacology, University of Cambridge, U.K.
Biochemical Society Transactions
|May 24, 2011
Summary
Multidrug transporters, like ABC transporters, export drugs from cells, causing resistance in microbes and tumors. Recent studies reveal a common mechanism involving ATP-driven domain changes that expose drug-binding sites.
Area of Science:
- Biochemistry
- Structural Biology
- Molecular Biology
Background:
- Multidrug transporters are key to drug resistance in microbes and tumors.
- These integral membrane proteins export diverse compounds, reducing intracellular drug levels.
- The precise mechanism of multidrug transporter action remains incompletely understood.
Purpose of the Study:
- To review recent advancements in the biochemistry and structural biology of multidrug ABC transporters.
- To elucidate the common working mechanism of bacterial and human multidrug ABC transporters.
Main Methods:
- Review of recent biochemical and structural biology studies.
- Analysis of ATP-binding cassette (ABC) transporter mechanisms.
Main Results:
- Identified a common mechanism for multidrug ABC transporters.
- Mechanism involves alternating exposure of polyspecific drug-binding surfaces.
- ATP-driven dimerization and dissociation of nucleotide-binding domains are crucial.
Conclusions:
- A unified model for multidrug transporter function is emerging.
- Understanding this mechanism can inform strategies to overcome drug resistance.
- Further research into ABC transporter dynamics is warranted.
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