Mechanism of anion exchange and small-molecule inhibition of pendrin.

ABSTRACT: Pendrin (SLC26A4) is an anion exchanger that mediates bicarbonate (HCO₃^-) exchange for chloride (Cl^-) and is crucial for maintaining pH and salt homeostasis in the kidney, lung, and cochlea. Pendrin also exports iodide (I^-) in the thyroid gland. Pendrin mutations in humans lead to Pendred syndrome, causing hearing loss and goiter. Inhibition of pendrin is a validated approach for attenuating airway hyperresponsiveness in asthma and for treating hypertension. However, the mechanism of anion exchange and its inhibition by drugs remains poorly understood. We applied cryo-electron microscopy to determine structures of pendrin from Sus scrofa in the presence of either Cl^-, I^-, HCO₃^- or in the apo-state. The

SUBMITTER: Wang L 

PROVIDER: S-EPMC10771415 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature