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P-glycoprotein structure and evolutionary homologies

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Multiple Drug Resistance in Cancer 2

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Abstract

Analysis of multidrug resistant cell lines has led to the identification of the P-glycoprotein multigene family. Two of the three classes of mammalian P-glycoproteins have the ability to confer cellular resistance to a broad range of structurally and functionally diverse cytotoxic agents. P-glycoproteins are integral membrane glycoproteins comprised of two similar halves, each consisting of six membrane spanning domains followed by a cytoplasmic domain which includes a nucleotide binding fold. The P-glycoprotein is a member of a large superfamily of transport proteins which utilize ATP to translocate a wide range of substrates across biological membranes. This superfamily includes transport complexes comprised of multicomponent systems, half P-glycoproteins and P-glycoprotein-like homologs which appear to require approximately 12 α-helical transmembrane domains and two nucleotide binding folds for substrate transport. P-glycoprotein homologs have been isolated and characterized from a wide range of species. Amino acid sequences, the similarities between the halves and intron/exon boundaries have been compared to understand the evolutionary origins of the P-glycoprotein.

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Authors and Affiliations

  1. The Dana-Faber Cancer Institute, Harvard Medical School, Boston, MA, USA

    Irene Bosch

  2. The Section of Pediatric Hematology/Oncology, James Whitcomb Riley Hospital for Children, Indiana University, Indianapolis, IN, 46202, USA

    James M. Croop MD, PhD

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  1. Irene Bosch
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  1. National Cell & Tissue Center, Bioresearch Ireland, Dublin City University, Glasnevin, Dublin, Ireland

    Martin Clynes

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Bosch, I., Croop, J.M. (1998). P-glycoprotein structure and evolutionary homologies. In: Clynes, M. (eds) Multiple Drug Resistance in Cancer 2. Springer, Dordrecht. https://doi.org/10.1007/978-94-017-2374-9_1

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