The First Cytoplasmic Loop in the Core Structure of the ABCC1 (Multidrug Resistance Protein 1; MRP1) Transporter Contains Multiple Amino Acids Essential for Its Expression.

ABSTRACT: ABCC1 (human multidrug resistance protein 1 (hMRP1)) is an ATP-binding cassette transporter which effluxes xeno- and endobiotic organic anions and confers multidrug resistance through active drug efflux. The 17 transmembrane α-helices of hMRP1 are distributed among three membrane spanning domains (MSD0, 1, 2) with MSD1,2 each followed by a nucleotide binding domain to form the 4-domain core structure. Eight conserved residues in the first cytoplasmic loop (CL4) of MSD1 in the descending α-helix (Gly³⁹², Tyr⁴⁰⁴, Arg⁴⁰⁵), the perpendicular coupling helix (Asn⁴¹², Arg⁴¹⁵, Lys⁴¹⁶), and the ascending α-helix (Glu⁴²², Phe⁴³⁴) were targeted for mutagenesis. Mutants with both alanine and same charge substitutio

SUBMITTER: Conseil G 

PROVIDER: S-EPMC8469891 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature