|Entry||Database: PDB / ID: 7yg1|
|Title||Cryo-EM structure of the C-terminal domain of the human sodium-chloride cotransporter|
|Components||Solute carrier family 12 member 3|
|Keywords||MEMBRANE PROTEIN / transporter / cation-chloride cotransporter|
|Function / homology|
Function and homology information
Defective SLC12A3 causes Gitelman syndrome (GS) / sodium:chloride symporter activity / sodium ion transmembrane transporter activity / sodium:potassium:chloride symporter activity / cellular response to inorganic substance / sodium ion homeostasis / Cation-coupled Chloride cotransporters / potassium:chloride symporter activity / chloride ion homeostasis / cell volume homeostasis ...Defective SLC12A3 causes Gitelman syndrome (GS) / sodium:chloride symporter activity / sodium ion transmembrane transporter activity / sodium:potassium:chloride symporter activity / cellular response to inorganic substance / sodium ion homeostasis / Cation-coupled Chloride cotransporters / potassium:chloride symporter activity / chloride ion homeostasis / cell volume homeostasis / potassium ion homeostasis / response to aldosterone / sodium ion transport / potassium ion import across plasma membrane / response to dietary excess / sodium ion transmembrane transport / chloride transmembrane transport / monoatomic ion transport / apical plasma membrane / protein phosphorylation / signal transduction / extracellular exosome / membrane / plasma membrane / cytosol
Similarity search - Function
Thiazide-sensitive Na-K-Cl co-transporter / Amino acid permease, N-terminal / Amino acid permease N-terminal / SLC12A transporter family / SLC12A transporter, C-terminal / Solute carrier family 12 / Amino acid permease/ SLC12A domain / Amino acid permease
Similarity search - Domain/homology
Solute carrier family 12 member 3
Similarity search - Component
|Biological species||Homo sapiens (human)|
|Method||ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.77 Å|
|Authors||Nan, J. / Yang, X.M. / Shan, Z.Y. / Yuan, Y.F. / Zhang, Y.Q.|
|Funding support|| China, 1items |
|Citation||Journal: Sci Adv / Year: 2022|
Title: Cryo-EM structure of the human sodium-chloride cotransporter NCC.
Authors: Jing Nan / Yafei Yuan / Xuemei Yang / Ziyang Shan / Huihui Liu / Feiwen Wei / Wei Zhang / Yanqing Zhang /
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 ...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.
|Structure viewer||Molecule: |
Downloads & links
A: Solute carrier family 12 member 3
B: Solute carrier family 12 member 3
Mass: 116921.461 Da / Num. of mol.: 2 / Mutation: A264G
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Cell line (production host): HEK293 / Production host: Homo sapiens (human) / References: UniProt: P55017
|Experiment||Method: ELECTRON MICROSCOPY|
|EM experiment||Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction|
|Component||Name: Sodium-chloride cotransporter / Type: COMPLEX / Entity ID: all / Source: RECOMBINANT|
|Molecular weight||Experimental value: NO|
|Source (natural)||Organism: Homo sapiens (human)|
|Source (recombinant)||Organism: Homo sapiens (human) / Cell: HEK293|
|Buffer solution||pH: 8|
|Specimen||Conc.: 9 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES|
|Vitrification||Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 281 K|
-Electron microscopy imaging
Model: Titan Krios / Image courtesy: FEI Company
|Microscopy||Model: FEI TITAN KRIOS|
|Electron gun||Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM|
|Electron lens||Mode: BRIGHT FIELDBright-field microscopy / Nominal magnification: 81000 X / Nominal defocus max: 2300 nm / Nominal defocus min: 1500 nm / Cs: 2.7 mm|
|Specimen holder||Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER|
|Image recording||Electron dose: 52.8 e/Å2 / Detector mode: SUPER-RESOLUTION / Film or detector model: GATAN K2 SUMMIT (4k x 4k)|
|EM imaging optics||Energyfilter name: GIF Quantum ER / Energyfilter slit width: 20 eV|
|CTF correction||Type: NONE|
|3D reconstruction||Resolution: 3.77 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 79225 / Symmetry type: POINT|
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