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A Salt Bridge in Intracellular Loop 2 Is Essential for Folding of Human P-Glycoprotein
[Image: see text] 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 th...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical
Society
2013
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3656768/ https://www.ncbi.nlm.nih.gov/pubmed/23634976 http://dx.doi.org/10.1021/bi400425k |
Sumario: | [Image: see text] 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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