8SZC

Heterodimeric ABC transporter BmrCD in the inward-facing conformation bound to substrate and ATP: BmrCD_IF-1HT/ATP

8SZC の概要

• エントリーDOI: 10.2210/pdb8szc/pdb
• EMDBエントリー: 29087 29297 29362 40908
• 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: transporter, complex, lipids, membrane protein, translocase
• 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: 162425.67

構造登録者

Tang, Q.,Mchaourab, H. (登録日: 2023-05-29, 公開日: 2023-11-15, 最終更新日: 2025-06-04)

主引用文献

Tang, Q.,Sinclair, M.,Hasdemir, H.S.,Stein, R.A.,Karakas, E.,Tajkhorshid, E.,Mchaourab, H.S.
Asymmetric conformations and lipid interactions shape the ATP-coupled cycle of a heterodimeric ABC transporter.
Nat Commun, 14:7184-7184, 2023

PubMed Abstract: Here we used cryo-electron microscopy (cryo-EM), double electron-electron resonance spectroscopy (DEER), and molecular dynamics (MD) simulations, to capture and characterize ATP- and substrate-bound inward-facing (IF) and occluded (OC) conformational states of the heterodimeric ATP binding cassette (ABC) multidrug exporter BmrCD in lipid nanodiscs. Supported by DEER analysis, the structures reveal that ATP-powered isomerization entails changes in the relative symmetry of the BmrC and BmrD subunits that propagates from the transmembrane domain to the nucleotide binding domain. The structures uncover asymmetric substrate and Mg binding which we hypothesize are required for triggering ATP hydrolysis preferentially in one of the nucleotide-binding sites. MD simulations demonstrate that multiple lipid molecules differentially bind the IF versus the OC conformation thus establishing that lipid interactions modulate BmrCD energy landscape. Our findings are framed in a model that highlights the role of asymmetric conformations in the ATP-coupled transport with general implications to the mechanism of ABC transporters.

PubMed: 37938578
DOI: 10.1038/s41467-023-42937-5

実験手法

ELECTRON MICROSCOPY (3.06 Å)