Structure and thiazide inhibition mechanism of the human Na-Cl cotransporter.

ABSTRACT: The sodium-chloride cotransporter (NCC) is critical for kidney physiology¹. The NCC has a major role in salt reabsorption in the distal convoluted tubule of the nephron^2,3, and mutations in the NCC cause the salt-wasting disease Gitelman syndrome⁴. As a key player in salt handling, the NCC regulates blood pressure and is the target of thiazide diuretics, which have been widely prescribed as first-line medications to treat hypertension for more than 60 years^5-7. Here we determined the structures of human NCC alone and in complex with a commonly used thiazide diuretic using cryo-electron microscopy. These structures, together with functional studies, reveal major conformational states of the NCC and an intriguing regulatory mechanism. They also ill

SUBMITTER: Fan M 

PROVIDER: S-EPMC10030352 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature