7yg1

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

spinqualitylabelsall models 7yg1, resolution 3.77Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7yg1 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.77Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease S12A3_HUMAN Gitelman syndrome. The disease is caused by variants affecting the gene represented in this entry. Function S12A3_HUMAN Electroneutral sodium and chloride ion cotransporter, which acts as a key mediator of sodium and chloride reabsorption in kidney distal convoluted tubules (PubMed:18270262, PubMed:21613606, PubMed:22009145, PubMed:36351028, PubMed:36792826). Also acts as a receptor for the pro-inflammatory cytokine IL18, thereby contributing to IL18-induced cytokine production, including IFNG, IL6, IL18 and CCL2 (By similarity). May act either independently of IL18R1, or in a complex with IL18R1 (By similarity).[UniProtKB:P59158] Publication Abstract from PubMed 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 A for the transmembrane domain and 3.8 A 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. Cryo-EM structure of the human sodium-chloride cotransporter NCC.,Nan J, Yuan Y, Yang X, Shan Z, Liu H, Wei F, Zhang W, Zhang Y Sci Adv. 2022 Nov 11;8(45):eadd7176. doi: 10.1126/sciadv.add7176. Epub 2022 Nov , 9. PMID:36351028 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Solute carrier family 12 3D structures

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