Rocker-Switch Mechanism of Choline Transmembrane Transport in FLVCR2: Dynamic Latch Residues and Cooperative Regulation of Transmembrane Helices.

ABSTRACT: As a key member of the major facilitator superfamily, FLVCR2 plays a crucial role in choline transport. However, the kinetic mechanism and substrate recognition mode of its transmembrane transport remain elusive. Here, we integrate long-time-scale molecular dynamics simulations, potential of mean force, and functional validation of a key substrate-anchoring residue to elucidate the complete conformational cycle and energy regulation network of FLVCR2 at the atomic level, revealing its characteristic "rocker-switch" mechanism. We find that choline transmembrane transport is synergistically regulated by the electrostatic environment and hydrophobic surface of the extracellular tunnel, ensuring stable substrate migration within the channel lumen and efficient entry into the binding site. A ne

SUBMITTER: Zhao X 

PROVIDER: S-EPMC12569663 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature