title: A salt bridge in intracellular loop 2 is essential for folding of human p-glycoprotein.
abstract: There is no high-resolution structure of the human P-glycoprotein (P-gp, ABCB1) drug pump. Homology models based on the crystal structures of mouse and Caenorhabditis elegans P-gps show extensive contacts between intracellular loop 2 (ICL2, in the first transmembrane domain) and the second nucleotide-binding domain. Human P-gp modeled on these P-gp structures yields different ICL2 structures. Only the model based on the C. elegans P-gp structure predicts the presence of a salt bridge. We show that the Glu256-Arg276 salt bridge was critical for P-gp folding.
authors: Departments of Medicine and Biochemistry, University of Toronto , Toronto, Ontario M5S 1A8, Canada.
authors: Tip W
authors: TW
authors: Loo
authors: David M
authors: DM
authors: Clarke
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000737:chemistry* / Q000235:genetics; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000235:genetics; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D017510:Protein Folding; D054730:Protein Interaction Domains and Motifs; D012492:Salts / Q000737:chemistry; D017386:Sequence Homology, Amino Acid; D040681:Structural Homology, Protein
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D029742:Caenorhabditis elegans Proteins; D012492:Salts
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