Structures of ABCB4 provide insight into phosphatidylcholine translocation

Significance ABCB4 is an ATP-binding cassette transporter expressed in hepatocytes and is essential for the formation of bile by translocating phosphatidylcholine into canaliculi. Mutations in ABCB4 can cause inherited diseases leading to cholestasis. Similarly, commonly used drugs interfering with ABCB4 function can cause drug-induced liver injury. We present cryogenic electron microscopy structures that reveal how ABCB4 recruits phosphatidylcholine from the lipid bilayer and translocates it into bile canaliculi and how this process is inhibited by the antifungal drug posaconazole.