ArticleScience advances2022
Cryo-EM structure of the human sodium-chloride cotransporter NCC.
Article in Science advances, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 30 citations in OpenAlex.
- Exploring the Role of the SLC12A Cation-Coupled Chloride Cotransporters in the Cardiovascular System.Cells · 2026Review
- Structural basis for the ion selectivity of potassium-chloride cotransporter KCC4 revealed by cryo-EM titration.Biophysics reports · 2026Article
- Bridging structure and function: artificial intelligence-based modelling of kidney proteins.Nature reviews. Nephrology · 2026Review
- The SLC-ome of membrane transport: From molecular discovery to physiology and clinical applications.Physiological reviews · 2025Review
- Transport and thiazide-inhibition mechanisms of the Na-Cl cotransporter: a structural perspective.Current opinion in nephrology and hypertension · 2025Review
- Molecular mechanisms of thiazide-like diuretics-mediated inhibition of the human Na-Cl cotransporter.Nature communications · 2025Article
- Drug inhibition and substrate transport mechanisms of human VMAT2.Nature communications · 2025Article
- Highly conserved ion binding sites are not all functionally relevant in mouse KCC4.Frontiers in molecular biosciences · 2025Article
- Sodium Chloride Cotransporter in Hypertension.Biomedicines · 2024Review
- Structural bases for NaNature communications · 2024Article
- Navigating the multifaceted intricacies of the NaPhysiological reviews · 2024Review
- Molecular mechanisms of NaBiophysical journal · 2024Article
- Case report: Two novel compound heterozygous variant ofFrontiers in genetics · 2024Article
- The role ofJournal of pharmaceutical analysis · 2023Review
- Cryo-EM structures of human organic anion transporting polypeptide OATP1B1.Cell research · 2023Article
- Thirty years of the NaCl cotransporter: from cloning to physiology and structure.American journal of physiology. Renal physiology · 2023Review
- Structure-function relationships in the sodium chloride cotransporter.Frontiers in physiology · 2023Review
- Editorial: 30th anniversary of the molecular cloning and identification of the Na-Cl cotransporter, NCC.Frontiers in physiology · 2023Article
- Structural Pharmacology of Cation-Chloride Cotransporters.Membranes · 2022Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.