Placing steroid hormones within the human ABCC3 transporter reveals a compatible amphiphilic substrate-binding pocket

ABSTRACT: The human ABC transporter ABCC3 (also known as MRP3) transports a wide spectrum of substrates, including endogenous metabolites and exogenous drugs. Accordingly, it participates in multiple physiological processes and is involved diverse human diseases such as intrahepatic cholestasis of pregnancy, which is caused by the intracellular accumulation of bile acids and estrogens. Here, we report three cryogenic electron microscopy structures of ABCC3: in the apo-form, and in complexed forms bound to either the conjugated sex hormones β-estradiol 17-(β-D-glucuronide) and dehydroepiandrosterone sulfate. For both hormones, the steroid nuclei that superimpose against each other occupy the hydrophobic center of the transport cavity, whereas the two conjugation groups are separated and fixed by the

SUBMITTER: Dr. Jie Wang 

PROVIDER: S-SCDT-10_15252-EMBJ_2022113415 | biostudies-other |

REPOSITORIES: biostudies-other