Structural insights into binding-site access and ligand recognition by human ABCB1

ABSTRACT: ABCB1 is a broad-spectrum efflux pump central to cellular drug handling and multidrug resistance in humans. However, how it is able to recognise and transport a wide range of diverse substrates remains poorly understood. Here we present cryo-EM structures of lipid-embedded human ABCB1 in conformationally distinct apo-, substrate-bound, inhibitor-bound, and nucleotide-trapped states at 3.4-3.9 Å resolution, in the absence of stabilizing antibodies or mutations. The substrate-binding site is located within one half of the molecule and, in the apo-state, is obstructed by transmembrane helix (TM) 4. Substrate and inhibitor binding are distinguished by major TM re-arrangements and their ligand binding chemistry, with TM4 playing a central role in all conformational transitions. Furthermore, our

SUBMITTER: Devanshu Kurre 

PROVIDER: S-SCDT-10_1038-S44318-025-00361-Z | biostudies-other |

REPOSITORIES: biostudies-other