[3P-1] ポスター3（3P-01ー3P-47）

[3P-38] SLC26A9トランスポーターの分子動力学シミュレーションが明らかにした、塩化物イオン輸送経路のゲート開閉運動における細胞質ドメインの役割

^○大森 聡¹, 花園 祐矢², 西 羽美^1,3, 木下 賢吾^1,4,5 (1.東北大・院・情報・応用・生命, 2.量研・量子生命, 3.お茶の水大・基幹研究院, 4.東北大・メディカルメガバンク, 5.東北大・加齢研)

Solute Carrier family 26 member A9 (SLC26A9) is a membrane-transport protein that exhibits chloride transporter activity and plays essential roles in many physiological processes such as airway surface hydration and gastric acid production. SLC26A9 has also been proposed as a potential target for the treatment of cystic fibrosis. The cryo-EM structures of homo-dimeric murine SLC26A9 in an inward-facing state and an intermediate state suggest a unique chloride transport mechanism: the cytoplasmic (STAS) domain mediates the interactions between the subunits. In a more recent study, the high-resolution cryo-EM structure of overall human SLC26A9 in an inward-facing state was reported. However, the detailed mechanism and role of the STAS domain are still unknown.In this study, we performed the MD simulations of SLC26A9 with the full-length (FL) model and the STAS domain removal (ΔSTAS) model. In the FL model, the overall motion of the STAS domain was cooperative to the gate opening motion of the chloride transport pathways during the simulation. In contrast, the gating motions were not observed in the ΔSTAS model. These results indicate that the role of the STAS domain is to promote ion transport by its rigid body like motion.