A salt bridge in intracellular loop 2 is essential for folding of human p-glycoprotein.

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  • Author(s): Loo TW;Loo TW; Clarke DM
  • Source:
    Biochemistry [Biochemistry] 2013 May 14; Vol. 52 (19), pp. 3194-6. Date of Electronic Publication: 2013 May 03.
  • Publication Type:
    Journal Article; Research Support, Non-U.S. Gov't
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: American Chemical Society Country of Publication: United States NLM ID: 0370623 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1520-4995 (Electronic) Linking ISSN: 00062960 NLM ISO Abbreviation: Biochemistry Subsets: MEDLINE
    • Publication Information:
      Original Publication: Washington, American Chemical Society.
    • Subject Terms:
      ATP Binding Cassette Transporter, Subfamily B, Member 1/*chemistry; ATP Binding Cassette Transporter, Subfamily B, Member 1/genetics ; Amino Acid Sequence ; Amino Acid Substitution ; Animals ; Caenorhabditis elegans Proteins/chemistry ; Caenorhabditis elegans Proteins/genetics ; Humans ; Mice ; Models, Molecular ; Molecular Sequence Data ; Mutagenesis, Site-Directed ; Protein Folding ; Protein Interaction Domains and Motifs ; Salts/chemistry ; Sequence Homology, Amino Acid ; Structural Homology, Protein
    • 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.
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    • Grant Information:
      25043 Canada Canadian Institutes of Health Research
    • Accession Number:
      0 (ATP Binding Cassette Transporter, Subfamily B, Member 1)
      0 (Caenorhabditis elegans Proteins)
      0 (Salts)
    • Publication Date:
      Date Created: 20130503 Date Completed: 20140210 Latest Revision: 20211021
    • Publication Date:
      20240829
    • Accession Number:
      PMC3656768
    • Accession Number:
      10.1021/bi400425k
    • Accession Number:
      23634976