9DXO

Cryo-EM structure of human OATP1C1 F240A mutant in complex with estrone 3-sulfate

9DXO の概要

• エントリーDOI: 10.2210/pdb9dxo/pdb
• EMDBエントリー: 47293
• 分子名称: Solute carrier organic anion transporter family member 1C1, estrone 3-sulfate (2 entities in total)
• 機能のキーワード: slc transporter, e1s, 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: 83514.51

構造登録者

Ge, Y.,Yadav, G.P.,Jiang, J.,Huang, P. (登録日: 2024-10-11, 公開日: 2025-07-16, 最終更新日: 2025-10-15)

主引用文献

Ge, Y.,Dou, T.,Nguyen, T.U.,Yadav, G.P.,Wensel, T.G.,Jiang, J.,Huang, P.
Structural insights into brain thyroid hormone transport via MCT8 and OATP1C1.
Cell, 188:5576-, 2025

PubMed Abstract: Adequate delivery of thyroid hormones to the brain is crucial for normal neurological development. MCT8 and OATP1C1, two solute carrier (SLC) transporters, mediate the passage of thyroid hormones across the blood-brain barrier and into the central nervous system. Mutations in MCT8 result in Allan-Herndon-Dudley syndrome (AHDS), an X-linked birth defect characterized by neurodevelopmental impairments and peripheral hyperthyroidism, whereas OATP1C1 deficiency is linked to brain hypometabolism and progressive neurodegeneration. Here, we report cryoelectron microscopy (cryo-EM) structures of MCT8 and OATP1C1 bound with the active thyroid hormone triiodothyronine (T3) and the prohormone thyroxine (T4) at 2.9 and 2.3 Å resolutions, respectively. Combined with functional studies, we elucidate their distinct thyroid hormone recognition and transport mechanisms and explain disease mutations. Although extracellular allosteric sites are not a common feature of SLC transporters, we identify one in OATP1C1. Collectively, these findings illuminate key aspects of thyroid hormone transport, a fundamental process in development and disease.

PubMed: 40680733
DOI: 10.1016/j.cell.2025.06.032

実験手法

ELECTRON MICROSCOPY (2.6 Å)