8FHO
Cryo-EM structure of human NCC (class 1)
Summary for 8FHO
| Entry DOI | 10.2210/pdb8fho/pdb |
| EMDB information | 29097 |
| Descriptor | Solute carrier family 12 member 2,Solute carrier family 12 member 3 chimera, ADENOSINE-5'-TRIPHOSPHATE, Polythiazide, ... (4 entities in total) |
| Functional Keywords | membrane transporter, membrane protein |
| Biological source | Danio rerio (Zebrafish, Brachydanio rerio) More |
| Total number of polymer chains | 3 |
| Total formula weight | 363056.60 |
| Authors | |
| Primary citation | Fan, M.,Zhang, J.,Lee, C.L.,Zhang, J.,Feng, L. Structure and thiazide inhibition mechanism of the human Na-Cl cotransporter. Nature, 614:788-793, 2023 Cited by PubMed Abstract: The sodium-chloride cotransporter (NCC) is critical for kidney physiology. The NCC has a major role in salt reabsorption in the distal convoluted tubule of the nephron, and mutations in the NCC cause the salt-wasting disease Gitelman syndrome. 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. 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 illuminate how thiazide diuretics specifically interact with the NCC and inhibit its transport function. Our results provide critical insights for understanding the Na-Cl cotransport mechanism of the NCC, and they establish a framework for future drug design and for interpreting disease-related mutations. PubMed: 36792826DOI: 10.1038/s41586-023-05718-0 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.95 Å) |
Structure validation
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