ArticleScience advances2020
Structures and an activation mechanism of human potassium-chloride cotransporters.
Article in Science advances, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 65 citations in OpenAlex.
- Regulated degradation of KCC2, a potassium-chloride co-transporter required for synaptic transmission and neurodevelopment.Channels (Austin, Tex.) · 2026Review
- Comparative Evolution of SLC12 Transporters in Tilapias and Salinity-Responsive Expression in Nile Tilapia.International journal of molecular sciences · 2026Article
- Structural basis for the ion selectivity of potassium-chloride cotransporter KCC4 revealed by cryo-EM titration.Biophysics reports · 2026Article
- Sheep erythrocyte potassium locus highlights MYADM family regulation of electroneutral potassium chloride cotransporters (KCC).BMC genomics · 2026Article
- Chasing the ghost in the code: highlighting the mystery of a rare genetic condition.American journal of physiology. Cell physiology · 2026Review
- Structural basis for pH-responsive amino acid transport via SLC7A4.Nature communications · 2026Article
- Spectrum of dominant Charcot-Marie-Tooth disease due toJournal of neurology, neurosurgery, and psychiatry · 2026Article
- Enhancing KCC2 function reduces interictal activity and prevents seizures in temporal lobe epilepsy.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Functional recovery induced by KCC2-enabled relay pathways in completely injured spinal cords in adult rats.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Structural basis of specific lysine transport by Pseudomonas aeruginosa permease LysP.Nature communications · 2025Article
- Medical and Nonmedical Applications of Synthetic Transmembrane Anion Transporters.Chemical reviews · 2025Review
- Biophysical characterization and ion transport with cell-based and proteoliposome reconstitution assays of invertebrate KFEBS open bio · 2025Article
- Molecular mechanisms of thiazide-like diuretics-mediated inhibition of the human Na-Cl cotransporter.Nature communications · 2025Article
- Probing the Reversible Binding of Anionic Reactive Sulfur and Nitrogen Species in Imidazolium Receptors with Directional C-H Hydrogen Bonds.Inorganic chemistry · 2025Article
- Flexibility-Induced Collective Behavior Drives Symmetry Breaking in Discrimination of Undesired Ions.JACS Au · 2025Article
- Highly conserved ion binding sites are not all functionally relevant in mouse KCC4.Frontiers in molecular biosciences · 2025Article
- Article
- Structure and mechanism of the osmoregulated choline transporter BetT.Science advances · 2024Article
- Impact of aging on the GABAbioRxiv : the preprint server for biology · 2024Article
- Gut commensal metabolite rhamnose promotes macrophages phagocytosis by activating SLC12A4 and protects against sepsis in mice.Acta pharmaceutica Sinica. B · 2024Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
Potassium-chloride cotransporters KCC1 to KCC4 mediate the coupled export of potassium and chloride across the plasma membrane and play important roles in cell volume regulation, auditory system function, and γ-aminobutyric acid (GABA) and glycine-mediated inhibitory neurotransmission. Here, we present 2.9- to 3.6-Å resolution structures of full-length human KCC2, KCC3, and KCC4. All three KCCs adopt a similar overall architecture, a domain-swap dimeric assembly, and an inward-facing conformation. The structural and functional studies reveal that one unexpected N-terminal peptide binds at the cytosolic facing cavity and locks KCC2 and KCC4 at an autoinhibition state. The C-terminal domain (CTD) directly interacts with the N-terminal inhibitory peptide, and the relative motions between the CTD and the transmembrane domain (TMD) suggest that CTD regulates KCCs' activities by adjusting the autoinhibitory effect. These structures provide the first glimpse of full-length structures of KCCs and an autoinhibition mechanism among the amino acid-polyamine-organocation transporter superfamily.
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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.