7ch1 | pdb_00007ch1
The overall structure of SLC26A9
Structural highlights
Function[S26A9_HUMAN] DIDS- and thiosulfate- sensitive anion exchanger mediating chloride, sulfate and oxalate transport (PubMed:11834742). Mediates chloride/bicarbonate exchange or chloride-independent bicarbonate extrusion thus assuring bicarbonate secretion (PubMed:15800055). May prefer chloride anions and mediate uncoupled chloride anion transport in an alternate-access mechanism where a saturable binding site is alternately exposed to either one or the other side of the membrane (By similarity).[UniProtKB:Q8BU91][1] [2] Publication Abstract from PubMedThe human SLC26 transporter family exhibits various transport characteristics, and family member SLC26A9 performs multiple roles, including acting as Cl(-)/HCO3 (-) 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 A 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. Structural insights into the gating mechanism of human SLC26A9 mediated by its C-terminal sequence.,Chi X, Jin X, Chen Y, Lu X, Tu X, Li X, Zhang Y, Lei J, Huang J, Huang Z, Zhou Q, Pan X Cell Discov. 2020 Aug 10;6:55. doi: 10.1038/s41421-020-00193-7. eCollection 2020. PMID:32818062[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||||
