8ZKO

CryoEM structure of Thyroid Hormone Transporter MCT8

8ZKO の概要

• エントリーDOI: 10.2210/pdb8zko/pdb
• EMDBエントリー: 60201
• 分子名称: Monocarboxylate transporter 8, 3,5,3'TRIIODOTHYRONINE, 1,2-DIACYL-SN-GLYCERO-3-PHOSPHOCHOLINE (3 entities in total)
• 機能のキーワード: mct8, slc16a2, membrane protein
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 121210.21

構造登録者

Tan, J.,Xiao, Y.,Kong, F.,Zhu, A.,Qian, J.,Yan, C. (登録日: 2024-05-17, 公開日: 2025-04-02, 最終更新日: 2025-07-02)

主引用文献

Tan, J.,Xiao, Y.,Kong, F.,Qian, J.,Zhu, A.,Yan, C.
Structural insights into thyroid hormone transporter MCT8.
Nat Commun, 16:2958-2958, 2025

PubMed Abstract: Thyroid hormones (THs), including T4 (3,5,3',5'-tetraiodo-L-thyronine) and T3 (3,5,3'-triiodo-L-thyronine), play critical roles in regulating tissue development and basal metabolism. Monocarboxylate transporter 8 (MCT8) is a key player in TH transport, known for its high specificity and affinity for THs and its direct association with Allan-Herndon-Dudley syndrome (AHDS) caused by pathogenic mutations. In this study, we present the cryo-EM structures of human MCT8 bound to the substrate T3 or the inhibitor silychristin, both in an outward-open conformation at resolutions of 3.0-3.2 Å. MCT8 forms a homodimer with a lipid molecule positioned at the dimerization interface. The carboxyl group of T3 is recognized by Arg371, while its three iodine atoms interact with distinct hydrophobic cavities. Silychristin is also recognized by Arg371, competing with T3 for binding. Complemented by structure-guided biochemical analyses, our research elucidates the mechanisms of substrate recognition and transport, as well as the mode of action of the inhibitor silychristin. These findings may offer insights for developing targeted therapies for TH-related disorders.

PubMed: 40140416
DOI: 10.1038/s41467-025-58131-8

実験手法

ELECTRON MICROSCOPY (3.13 Å)