9CTF

SapNP Reconstituted Human ABCB1 bound to Taxol in presence of ATP

9CTF の概要

• エントリーDOI: 10.2210/pdb9ctf/pdb
• 関連するPDBエントリー: 9CR8 9CTC
• EMDBエントリー: 45854 45903 45904
• 分子名称: ATP-dependent translocase ABCB1, UNKNOWN BRANCHED FRAGMENT OF PHOSPHOLIPID, ADENOSINE-5'-TRIPHOSPHATE, ... (4 entities in total)
• 機能のキーワード: abcb1, p-gp, substrate bound, nanoparticle, saposin a, taxol bound, membrane protein, php, mdr1, translocase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 153542.11

構造登録者

Kurre, D.,Alam, A. (登録日: 2024-07-25, 公開日: 2025-01-22, 最終更新日: 2025-05-21)

主引用文献

Kurre, D.,Dang, P.X.,Le, L.T.M.,Gadkari, V.V.,Alam, A.
Structural insights into binding-site access and ligand recognition by human ABCB1.
Embo J., 44:991-1006, 2025

PubMed Abstract: ABCB1 is a broad-spectrum efflux pump central to cellular drug handling and multidrug resistance in humans. However, how it is able to recognize 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 the transmembrane helix (TM) 4. Substrate and inhibitor binding are distinguished by major TM rearrangements and their ligand binding chemistry, with TM4 playing a central role in all conformational transitions. Furthermore, our data identify secondary structure-breaking residues that impart localized TM flexibility and asymmetry between the two transmembrane domains. The resulting structural changes and lipid interactions that are induced by substrate and inhibitor binding can predict substrate-binding profiles and may direct ABCB1 inhibitor design.

PubMed: 39806099
DOI: 10.1038/s44318-025-00361-z

実験手法

ELECTRON MICROSCOPY (3.9 Å)