title: P-glycoprotein structure and evolutionary homologies.
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 12 alpha-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.
authors.affiliation: Division of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA.
authors.forename: J M
authors.initials: JM
authors.lastname: Croop
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000595:Amino Acid Sequence; D000818:Animals; D005075:Biological Evolution; D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics*; D002460:Cell Line; D006224:Cricetinae; D018076:DNA, Complementary / Q000302:isolation & purification / Q000378:metabolism; D004330:Drosophila / Q000235:genetics; D004351:Drug Resistance / Q000235:genetics*; D056890:Eukaryota / Q000235:genetics; D006801:Humans; D008562:Membrane Glycoproteins / Q000737:chemistry* / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D010802:Phylogeny; D010944:Plants / Q000235:genetics; D017433:Protein Structure, Secondary; D012441:Saccharomyces cerevisiae / Q000235:genetics; D012568:Schizosaccharomyces / Q000235:genetics; D017386:Sequence Homology, Amino Acid
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002352:Carrier Proteins; D018076:DNA, Complementary; D008562:Membrane Glycoproteins