9LJH

Cryo-EM structure of human organic solute transporter OSTalpha/beta in complex with DHEAS

9LJH の概要

• エントリーDOI: 10.2210/pdb9ljh/pdb
• EMDBエントリー: 63149
• 分子名称: Organic solute transporter subunit alpha, Organic solute transporter subunit beta, PALMITIC ACID, ... (6 entities in total)
• 機能のキーワード: transport ad, transport protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 115521.43

構造登録者

Wang, K.,Jiang, D.H. (登録日: 2025-01-15, 公開日: 2025-12-03, 最終更新日: 2026-03-18)

主引用文献

Wang, K.,Fan, J.,Chen, H.,Huang, B.,Chi, C.,Yan, R.,Wu, D.,Zhou, F.,Zhang, W.,Jiang, J.,Lei, X.,Jiang, D.
Structure and mechanism of the human bile acid transporter OST alpha-OST beta.
Nature, 651:251-259, 2026

PubMed Abstract: Bile acids (BAs) are crucial amphipathic surfactants that function as multifaceted regulators in various physiological processes, including nutrient absorption and distribution, lipid metabolism and inflammation. The human organic solute transporter αβ (OSTα-OSTβ; hereafter referred to as OSTα/β) is a BA transporter that has a key role in the secretion and distribution of BAs. Pathogenic mutations in OSTα/β have been associated with cholestasis. Despite the functional importance of OSTα/β in BA homeostasis, the stoichiometry and assembly of the complex and the molecular mechanism that underlies BA transport by OSTα/β remain unknown. Here we present cryo-electron microscopy structures of human OSTα/β in complex with cholesterols and an endogenous substrate, elucidating the structural basis for the function of OSTα/β. OSTα/β is assembled in a novel dimer-of-heterodimers manner: two OSTα units form the homodimeric core, with two OSTβ units bound to the periphery. OSTα adopts the G-protein-coupled-receptor (GPCR) fold and contains a unique cysteine-rich loop with seven palmitoylation sites; these cooperate with transmembrane helices 5 and 6, constituting a BA recognition site. A positive cavity in OSTα connects the BA site and facilitates the transmembrane translocation of BAs through OSTα/β. Together, this study reveals the architecture and transport mechanism of OSTα/β and provides insights into the structure-function relationships of this crucial transporter in BA homeostasis.

PubMed: 41606314
DOI: 10.1038/s41586-025-09934-8

実験手法

ELECTRON MICROSCOPY (2.73 Å)