ArticleThe Journal of biological chemistry2014
Molecular motions involved in Na-K-Cl cotransporter-mediated ion transport and transporter activation revealed by internal cross-linking between transmembrane domains 10 and 11/12.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 21 citations in OpenAlex.
- The SLC-ome of membrane transport: from molecular discovery to physiology and clinical applications.Physiological reviews · 2026Review
- Cation Chloride Cotransporter NKCC1 Operates through a Rocking-Bundle Mechanism.Journal of the American Chemical Society · 2024Article
- Structure of the human cation-chloride cotransport KCC1 in an outward-open state.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Structural basis for inhibition of the Cation-chloride cotransporter NKCC1 by the diuretic drug bumetanide.Nature communications · 2022Article
- NKCC1 and KCC2: Structural insights into phospho-regulation.Frontiers in molecular neuroscience · 2022Review
- Repeated Sevoflurane Exposure in Neonatal Rats Enhances the Sensitivity to Pain and Traumatic Stress Later in Juvenile Life.Journal of pain research · 2022Article
- High-Resolution Views and Transport Mechanisms of the NKCC1 and KCC Transporters.Journal of molecular biology · 2021Review
- Molecular characteristics and physiological roles of NaJournal of cellular physiology · 2021Review
- The structural basis of function and regulation of neuronal cotransporters NKCC1 and KCC2.Communications biology · 2021Article
- Structure of the human cation-chloride cotransporter NKCC1 determined by single-particle electron cryo-microscopy.Nature communications · 2020Article
- Phosphoregulation of the intracellular termini of KThe Journal of biological chemistry · 2018Article
- Potentiating KCC2 activity is sufficient to limit the onset and severity of seizures.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Probing the proton channels in subunit N of Complex I from Escherichia coli through intra-subunit cross-linking.Biochimica et biophysica acta · 2016Article
- A novel regulatory locus of phosphorylation in the C terminus of the potassium chloride cotransporter KCC2 that interferes with N-ethylmaleimide or staurosporine-mediated activation.The Journal of biological chemistry · 2014Article
- Molecular and evolutionary insights into the structural organization of cation chloride cotransporters.Frontiers in cellular neuroscience · 2014Review
- The biogenesis of potassium transporters: implications of disease-associated mutations.Critical reviews in biochemistry and molecular biologyReview
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
We examined the relationship between transmembrane domain (TM) 10 and TM11/12 in NKCC1, testing homology models based on the structure of AdiC in the same transporter superfamily. We hypothesized that introduced cysteine pairs would be close enough for disulfide formation and would alter transport function: indeed, evidence for cross-link formation with low micromolar concentrations of copper phenanthroline or iodine was found in 3 of 8 initially tested pairs and in 1 of 26 additionally tested pairs. Inhibition of transport was observed with copper phenanthroline and iodine treatment of P676C/A734C and I677C/A734C, consistent with the proximity of these residues and with movement of TM10 during the occlusion step of ion transport. We also found Cu(2+) inhibition of the single-cysteine mutant A675C, suggesting that this residue and Met(382) of TM3 are involved in a Cu(2+)-binding site. Surprisingly, cross-linking of P676C/I730C was found to prevent rapid deactivation of the transporter while not affecting the dephosphorylation rate, thus uncoupling the phosphorylation and activation steps. Consistent with this, (a) cross-linking of P676C/I730C was dependent on activation state, and (b) mutants lacking the phosphoregulatory domain could still be activated by cross-linking. These results suggest a model of NKCC activation that involves movement of TM12 relative to TM10, which is likely tied to movement of the large C terminus, a process somehow triggered by phosphorylation of the regulatory domain in the N terminus.
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