Dissecting the Forces that Dominate Dimerization of the Nucleotide Binding Domains of ABCB1.

ABSTRACT: P-glycoprotein, also known as multidrug resistance protein 1 or ABCB1, can export a wide range of chemically unrelated compounds, including chemotherapeutic drugs. ABCB1 consists of two transmembrane domains that form the substrate binding and translocation domain, and of two cytoplasmic nucleotide binding domains (NBDs) that energize substrate transport by ATP binding and hydrolysis. ATP binding triggers dimerization of the NBDs, which switches the transporter from an inward facing to an outward facing transmembrane domain conformation. We performed MD simulations to study the dynamic behavior of the NBD dimer in the presence or absence of nucleotides. In the apo configuration, the NBDs were overall attractive to each other as shown in the potential of mean force profile, but the energy w

SUBMITTER: Szollosi D 

PROVIDER: S-EPMC5984967 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature