National Natural Science Foundation of China (NSFC)
31800628
China
National Natural Science Foundation of China (NSFC)
31971123
China
Citation
Journal: Cell Discov / Year: 2020 Title: Structural insights into the gating mechanism of human SLC26A9 mediated by its C-terminal sequence. Authors: Ximin Chi / Xueqin Jin / Yun Chen / Xiaoli Lu / Xinyu Tu / Xiaorong Li / Yuanyuan Zhang / Jianlin Lei / Jing Huang / Zhuo Huang / Qiang Zhou / Xiaojing Pan / Abstract: The human SLC26 transporter family exhibits various transport characteristics, and family member SLC26A9 performs multiple roles, including acting as Cl/HCO exchangers, Cl channels, and Na ...The human SLC26 transporter family exhibits various transport characteristics, and family member SLC26A9 performs multiple roles, including acting as Cl/HCO exchangers, Cl channels, and Na transporters. Some mutations of SLC26A9 are correlated with abnormalities in respiration and digestion systems. As a potential target colocalizing with CFTR in cystic fibrosis patients, SLC26A9 is of great value in drug development. Here, we present a cryo-EM structure of the human SLC26A9 dimer at 2.6 Å resolution. A segment at the C-terminal end is bound to the entry of the intracellular vestibule of the putative transport pathway, which has been proven by electrophysiological experiments to be a gating modulator. Multiple chloride and sodium ions are resolved in the high-resolution structure, identifying novel ion-binding pockets for the first time. Together, our structure takes important steps in elucidating the structural features and regulatory mechanism of SLC26A9, with potential significance in the treatment of cystic fibrosis.
History
Deposition
Jul 3, 2020
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Header (metadata) release
Aug 26, 2020
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Map release
Aug 26, 2020
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Update
Mar 27, 2024
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Current status
Mar 27, 2024
Processing site: PDBj / Status: Released
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