Evidence for the critical role of transmembrane helices 1 and 7 in substrate transport by human P-glycoprotein (ABCB1).

ABSTRACT: P-glycoprotein (P-gp) is an ABC transporter that exports many amphipathic or hydrophobic compounds, including chemically and functionally dissimilar anticancer drugs, from cells. To understand the role of transmembrane helices (TMH) 1 and 7 in drug-binding and transport, we selected six residues from both TMH1 (V53, I59, I60, L65, M68 and F72) and TMH7 (V713, I719, I720, Q725, F728 and F732); and substituted them with alanine by gene synthesis to generate a variant termed "TMH1,7 mutant P-gp". The expression and function of TMH1,7 mutant P-gp with twelve mutations was characterized using the BacMam baculovirus-HeLa cell expression system. The expression and conformation of TMH1,7 mutant P-gp was not altered by the introduction of the twelve mutations, as confirmed by using the human P-gp-s

SUBMITTER: Sajid A 

PROVIDER: S-EPMC6161881 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature