3ZUX

Crystal structure of a bacterial homologue of the bile acid sodium symporter ASBT.

3ZUX の概要

• エントリーDOI: 10.2210/pdb3zux/pdb
• 関連するPDBエントリー: 3ZUY
• 分子名称: Transporter, SODIUM ION, MERCURY (II) ION, ... (7 entities in total)
• 機能のキーワード: transport protein, membrane protein
• 由来する生物種: Neisseria meningitidis
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 38658.66

構造登録者

Hu, N.-J.,Iwata, S.,Cameron, A.D.,Drew, D. (登録日: 2011-07-21, 公開日: 2011-10-12, 最終更新日: 2024-06-19)

主引用文献

Hu, N.-J.,Iwata, S.,Cameron, A.D.,Drew, D.
Crystal Structure of a Bacterial Homologue of the Bile Acid Sodium Symporter Asbt.
Nature, 478:408-, 2011

PubMed Abstract: High cholesterol levels greatly increase the risk of cardiovascular disease. About 50 per cent of cholesterol is eliminated from the body by its conversion into bile acids. However, bile acids released from the bile duct are constantly recycled, being reabsorbed in the intestine by the apical sodium-dependent bile acid transporter (ASBT, also known as SLC10A2). It has been shown in animal models that plasma cholesterol levels are considerably lowered by specific inhibitors of ASBT, and ASBT is thus a target for hypercholesterolaemia drugs. Here we report the crystal structure of a bacterial homologue of ASBT from Neisseria meningitidis (ASBT(NM)) at 2.2 Å. ASBT(NM) contains two inverted structural repeats of five transmembrane helices. A core domain of six helices harbours two sodium ions, and the remaining four helices pack in a row to form a flat, 'panel'-like domain. Overall, the architecture of the protein is remarkably similar to the sodium/proton antiporter NhaA, despite having no detectable sequence homology. The ASBT(NM) structure was captured with the substrate taurocholate present, bound between the core and panel domains in a large, inward-facing, hydrophobic cavity. Residues near this cavity have been shown to affect the binding of specific inhibitors of human ASBT. The position of the taurocholate molecule, together with the molecular architecture, suggests the rudiments of a possible transport mechanism.

PubMed: 21976025
DOI: 10.1038/NATURE10450

実験手法

X-RAY DIFFRACTION (2.2 Å)