Membrane-dependent dynamics and dual translocation mechanisms of ABCB4: Insights from molecular dynamics simulations.

ABSTRACT: ABCB4 is an ATP-binding cassette transporter expressed at the canalicular membrane of hepatocytes and responsible for translocating phosphatidylcholine into bile. Despite the recent cryo-EM structures of ABCB4, knowledge about the molecular mechanism of phosphatidylcholine transport remains fragmented. In this study, we used all-atom molecular dynamics simulations to investigate ABCB4 dynamics during its transport cycle, leveraging both symmetric and asymmetric membrane models. Our results demonstrate that membrane composition influences the local conformational dynamics of ABCB4, revealing distinct lipid-binding patterns across different conformers, particularly for cholesterol. We explored the two potential mechanisms for phosphatidylcholine translocation: the canonical ATP-driven altern

SUBMITTER: Crespi V 

PROVIDER: S-EPMC11979951 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature