7YG1

Cryo-EM structure of the C-terminal domain of the human sodium-chloride cotransporter

Summary for 7YG1

• Entry DOI: 10.2210/pdb7yg1/pdb
• Related: 7Y6I 7YG0
• EMDB information: 33641 33803 33804
• Descriptor: Solute carrier family 12 member 3 (1 entity in total)
• Functional Keywords: transporter, cation-chloride cotransporter, membrane protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 2
• Total formula weight: 233842.92

Authors

Nan, J.,Yang, X.M.,Shan, Z.Y.,Yuan, Y.F.,Zhang, Y.Q. (deposition date: 2022-07-09, release date: 2022-11-23, Last modification date: 2024-07-03)

Primary citation

Nan, J.,Yuan, Y.,Yang, X.,Shan, Z.,Liu, H.,Wei, F.,Zhang, W.,Zhang, Y.
Cryo-EM structure of the human sodium-chloride cotransporter NCC.
Sci Adv, 8:eadd7176-eadd7176, 2022

PubMed Abstract: The sodium-chloride cotransporter NCC mediates the coupled import of sodium and chloride across the plasma membrane, playing vital roles in kidney extracellular fluid volume and blood pressure control. Here, we present the full-length structure of human NCC, with 2.9 Å for the transmembrane domain and 3.8 Å for the carboxyl-terminal domain. NCC adopts an inward-open conformation and a domain-swap dimeric assembly. Conserved ion binding sites among the cation-chloride cotransporters and the Na2 site are observed in our structure. A unique His residue in the substrate pocket in NCC potentially interacts with Na1 and Cl1 and might also mediate the coordination of Na2 through a Ser residue. Putative observed water molecules are indicated to participate in the coordination of ions and TM coupling. Together with transport activity assays, our structure provides the first glimpse of NCC and defines ion binding sites, promoting drug development for hypertension targeting on NCC.

PubMed: 36351028
DOI: 10.1126/sciadv.add7176

Experimental method

ELECTRON MICROSCOPY (3.77 Å)