9CUR

BmrCD in the inward-facing conformation bound to Hoechsts and lipids

9CUR の概要

• エントリーDOI: 10.2210/pdb9cur/pdb
• 関連するPDBエントリー: 8FMV 8T1P
• EMDBエントリー: 29297 40974 45939
• 分子名称: Probable multidrug resistance ABC transporter ATP-binding/permease protein YheH, Probable multidrug resistance ABC transporter ATP-binding/permease protein YheI, (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate, ... (6 entities in total)
• 機能のキーワード: abc transporter, exporter, membrane protein, transport
• 由来する生物種: Bacillus subtilis subsp. subtilis str. 168; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 167522.82

構造登録者

Tang, Q.,Mchaourab, H.S. (登録日: 2024-07-26, 公開日: 2025-08-13, 最終更新日: 2025-12-03)

主引用文献

Tang, Q.,Sinclair, M.,Bisignano, P.,Zhang, Y.,Tajkhorshid, E.,Mchaourab, H.S.
Drug-bound outward-facing conformation of a heterodimeric ABC exporter suggests a putative mechanism of drug translocation.
Nat Commun, 16:10403-10403, 2025

PubMed Abstract: Multidrug transport by ATP binding cassette (ABC) exporters entails a mechanism to modulate drug affinity across the transport cycle. Here, we combine cryo-EM and molecular dynamics (MD) simulations to illuminate a lipid-competition mechanism to drive substrate translocation by ABC exporters. We determine cryo-EM structures of the ABC transporter BmrCD in drug-loaded inward-facing (IF) and outward-facing (OF) conformations in lipid nanodiscs to reveal the structural basis of alternating access, details of drug-transporter interactions, and the scale of drug movement between the two conformations. Remarkably, the structures uncover lipid molecules bound in or near the transporter vestibule along with the drugs. MD trajectories from the IF structure show that these lipids stimulate drug disorder and translocation towards the innermost constricted region of the vestibule. Similarly, bound lipids enter the OF vestibule and weaken drug-transporter interactions facilitating drug release. Our results complete a near-atomic model of BmrCD's conformational cycle and suggest the modulation of substrate-transporter interactions by lipids.

PubMed: 41285748
DOI: 10.1038/s41467-025-65318-6

実験手法

ELECTRON MICROSCOPY (3.4 Å)