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P-glycoprotein structure and evolutionary homologies

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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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  1. Harvard Medical School, The Dana-Faber Cancer Institute, Boston, MA, U.S.A

    Irene Bosch

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

    James M. Croop

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Bosch, I., Croop, J.M. P-glycoprotein structure and evolutionary homologies. Cytotechnology 27, 1–30 (1998). https://doi.org/10.1023/A:1008080911522

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