Novel features in the structure of P-glycoprotein (ABCB1) in the post-hydrolytic state as determined at 7.9 A resolution.

ABSTRACT:

Background

P-glycoprotein (ABCB1) is an ATP-binding cassette transporter that plays an important role in the clearance of drugs and xenobiotics and is associated with multi-drug resistance in cancer. Although several P-glycoprotein structures are available, these are either at low resolution, or represent mutated and/or quiescent states of the protein.

Results

In the post-hydrolytic state the structure of the wild-type protein has been resolved at about 8 Å resolution. The cytosolic nucleotide-binding domains (NBDs) are separated but ADP remains bound, especially at the first NBD. Gaps in the transmembrane domains (TMDs) that connect to an inner hydrophilic cavity are filled by density emerging from the annular detergent micelle. The NBD-TMD linker is partly resolved, being

SUBMITTER: Thonghin N 

PROVIDER: S-EPMC6293506 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature