[3P-1] Poster 3 (3P-01ー3P-47)

[3P-38] Gating motion mediated by the cytoplasmic domain of SLC26A9 in chloride ion transport revealed by the molecular dynamics simulations

^○Satoshi Omori¹, Yuya Hanazono², Hafumi Nishi^1,3, Kengo Kinoshita^1,4,5 (1.GSIS, Tohoku Univ., 2.Inst. for Quantum Life Sci., QST, 3.Faculty of Core Res., Ochanomizu Univ., 4.ToMMo, Tohoku Univ., 5.Inst. of Dev. Aging and Cancer, Tohoku Univ.)

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.