ArticleThe Journal of biological chemistry2009
Roles of two Ca2+-binding domains in regulation of the cardiac Na+-Ca2+ exchanger.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 83 citations in OpenAlex.
- Article
- Probing Charge-Controlled Inter-Domain Flexibility: Integrating Experimental and Coarse-Grained Approaches.Journal of chemical information and modeling · 2026Article
- The mechanism of action of digoxin requires the sodium-dependent inactivation of the sodium-calcium exchanger.Science advances · 2025Article
- Monocellular and Multicellular Parasites Infesting Humans: A Review of Calcium Ion Mechanisms.Biomedicines · 2025Review
- Structural mechanisms of PIPeLife · 2025Article
- Identification of a magnesium-binding site at the primary allosteric calcium sensor of the sodium-calcium exchanger: Implications for physiological regulation.Protein science : a publication of the Protein Society · 2024Article
- Cardiac function is regulated by the sodium-dependent inhibition of the sodium-calcium exchanger NCX1.Nature communications · 2024Article
- Structural mechanisms of the human cardiac sodium-calcium exchanger NCX1.Nature communications · 2023Article
- Proton-modulated interactions of ions with transport sites of prokaryotic and eukaryotic NCX prototypes.Cell calcium · 2021Article
- Insights into the molecular basis of the palmitoylation and depalmitoylation of NCX1.Cell calcium · 2021Article
- Dynamic Palmitoylation of the Sodium-Calcium Exchanger Modulates Its Structure, Affinity for Lipid-Ordered Domains, and Inhibition by XIP.Cell reports · 2020Article
- Modulation of the cardiac NaCell calcium · 2020Review
- Molecular determinants of pH regulation in the cardiac NaThe Journal of general physiology · 2018Article
- The Role of Sodium in Diabetic Cardiomyopathy.Frontiers in physiology · 2018Review
- An amphipathic α-helix directs palmitoylation of the large intracellular loop of the sodium/calcium exchanger.The Journal of biological chemistry · 2017Article
- Structure-based dynamic arrays in regulatory domains of sodium-calcium exchanger (NCX) isoforms.Scientific reports · 2017Article
- Discovery of Compounds that Positively Modulate the High Affinity Choline Transporter.Frontiers in molecular neuroscience · 2017Article
- Modeling NaJournal of molecular and cellular cardiology · 2016Article
- Electrophysiological characterization of the archaeal transporter NCX_Mj using solid supported membrane technology.The Journal of general physiology · 2016Article
- Protein Phosphatase 1c Associated with the Cardiac Sodium Calcium Exchanger 1 Regulates Its Activity by Dephosphorylating Serine 68-phosphorylated Phospholemman.The Journal of biological chemistry · 2016Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
We expressed full-length Na(+)-Ca(2+) exchangers (NCXs) with mutations in two Ca(2+)-binding domains (CBD1 and CBD2) to determine the roles of the CBDs in Ca(2+)-dependent regulation of NCX. CBD1 has four Ca(2+)-binding sites, and mutation of residues Asp(421) and Glu(451), which primarily coordinate Ca(2+) at sites 1 and 2, had little effect on regulation of NCX by Ca(2+). In contrast, mutations at residues Glu(385), Asp(446), Asp(447), and Asp(500), which coordinate Ca(2+) at sites 3 and 4 of CBD1, resulted in a drastic decrease in the apparent affinity of peak exchange current for regulatory Ca(2+). Another mutant, M7, with 7 key residues of CBD1 replaced, showed a further decrease in apparent Ca(2+) affinity but retained regulation, confirming a contribution of CBD2 to Ca(2+) regulation. Addition of the mutation K585E (located in CBD2) into the M7 background induced a marked increase in Ca(2+) affinity for both steady-state and peak currents. Also, we have shown previously that the CBD2 mutations E516L and E683V have no Ca(2+)-dependent regulation. We now demonstrate that introduction of a positive charge at these locations rescues Ca(2+)-dependent regulation. Finally, our data demonstrate that deletion of the unstructured loops between beta-strands F and G of both CBDs does not alter the regulation of the exchanger by Ca(2+), indicating that these segments are not important in regulation. Thus, CBD1 and CBD2 have distinct roles in Ca(2+)-dependent regulation of NCX. CBD1 determines the affinity of NCX for regulatory Ca(2+), although CBD2 is also necessary for Ca(2+)-dependent regulation.
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