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.

SUBMITTER: Loo TW 

PROVIDER: S-EPMC3656768 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature