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Structure–Function Analyses of Multidrug Transporters

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Candida albicans: Cellular and Molecular Biology

Abstract

Proteins catalysing the transport of molecules across biological membranes are vital for organisms in all kingdoms of life. These proteins are needed for the uptake of nutrients and the efflux of signalling molecules and toxic compounds. In the human opportunistic pathogen Candida albicans, efflux proteins can translocate antifungal drugs, such as fluconazole, and confer drug resistance. There are two main families of membrane proteins involved in drug transport, the major facilitator superfamily (MFS) and the ATP-binding cassette (ABC) proteins. Both types of protein possess multiple membrane spanning α-helices in transmembrane domains (TMDs), and ABC proteins, in addition, contain cytosolic nucleotide-binding domains (NBDs) involved in ATP hydrolysis. ABC proteins, and to a lesser extent MFS proteins, have broad substrate specificities that are determined by the structure and arrangement of the transmembrane α-helices. The multidrug transporter most often associated with drug resistance of C. albicans clinical isolates is ABC protein Cdr1. This is a pleiotropic drug resistance (PDR) ABC protein with domain arrangement NBD1-TMD1-NBD2-TMD2 and unique large extracellular loops between transmembrane α-helices that may be important for pump function. There is no crystal structure for Cdr1, but X-ray structures of related proteins indicate that unique interactions between conserved elements of the TMDs and the NBDs are important for pump function.

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Acknowledgements

The authors acknowledge financial support from the Marsden Fund of the Royal Society of New Zealand (UOO1305) and a research grant from Chulalongkorn University, Thailand.

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Authors and Affiliations

  1. Sir John Walsh Research Institute, Faculty of Dentistry, University of Otago, PO Box 56, Dunedin, 9054, New Zealand

    Erwin Lamping, Golnoush Madani, Hee Ji Lee, Masakazu Niimi & Richard D. Cannon

  2. Mycology Unit, Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand

    Masakazu Niimi

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  1. Erwin Lamping
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  2. Golnoush Madani
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  3. Hee Ji Lee
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  4. Masakazu Niimi
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  5. Richard D. Cannon
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Correspondence to Richard D. Cannon .

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  1. Amity Institute of Integrative Sciences and Health and Amity Institute of Biotechnology, Amity Institute of Integrative Sciences and Health and Amity Institute of Biotechnology, Amity University Haryana, Gurgaon, Haryana, India

    Rajendra Prasad

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Lamping, E., Madani, G., Lee, H.J., Niimi, M., Cannon, R.D. (2017). Structure–Function Analyses of Multidrug Transporters. In: Prasad, R. (eds) Candida albicans: Cellular and Molecular Biology. Springer, Cham. https://doi.org/10.1007/978-3-319-50409-4_18

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