6S7P

Nucleotide bound ABCB4

6S7P の概要

• エントリーDOI: 10.2210/pdb6s7p/pdb
• EMDBエントリー: 10111
• 分子名称: Phosphatidylcholine translocator ABCB4, ADENOSINE-5'-TRIPHOSPHATE, MAGNESIUM ION, ... (4 entities in total)
• 機能のキーワード: abc transporter, lipid extruder, transport protein
• 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: 144965.30

構造登録者

Olsen, J.A.,Alam, A.,Kowal, J.,Stieger, B.,Locher, K.P. (登録日: 2019-07-05, 公開日: 2019-12-25, 最終更新日: 2024-05-22)

主引用文献

Olsen, J.A.,Alam, A.,Kowal, J.,Stieger, B.,Locher, K.P.
Structure of the human lipid exporter ABCB4 in a lipid environment.
Nat.Struct.Mol.Biol., 27:62-70, 2020

PubMed Abstract: ABCB4 is an ATP-binding cassette transporter that extrudes phosphatidylcholine into the bile canaliculi of the liver. Its dysfunction or inhibition by drugs can cause severe, chronic liver disease or drug-induced liver injury. We determined the cryo-EM structure of nanodisc-reconstituted human ABCB4 trapped in an ATP-bound state at a resolution of 3.2 Å. The nucleotide binding domains form a closed conformation containing two bound ATP molecules, but only one of the ATPase sites contains bound Mg. The transmembrane domains adopt a collapsed conformation at the level of the lipid bilayer, but we observed a large, hydrophilic and fully occluded cavity at the level of the cytoplasmic membrane boundary, with no ligand bound. This indicates a state following substrate release but prior to ATP hydrolysis. Our results rationalize disease-causing mutations in human ABCB4 and suggest an 'alternating access' mechanism of lipid extrusion, distinct from the 'credit card swipe' model of other lipid transporters.

PubMed: 31873305
DOI: 10.1038/s41594-019-0354-3

実験手法

ELECTRON MICROSCOPY (3.2 Å)