ArticlePloS one2012
A common Ca2+-driven interdomain module governs eukaryotic NCX regulation.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 45 citations in OpenAlex.
- Article
- The NaThe Journal of veterinary medical science · 2026Review
- Probing Charge-Controlled Inter-Domain Flexibility: Integrating Experimental and Coarse-Grained Approaches.Journal of chemical information and modeling · 2026Article
- 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
- Structural dynamics of NaCommunications biology · 2024Article
- Structural insight into the allosteric inhibition of human sodium-calcium exchanger NCX1 by XIP and SEA0400.The EMBO journal · 2024Article
- Structural mechanisms of the human cardiac sodium-calcium exchanger NCX1.Nature communications · 2023Article
- Structure-Based Function and Regulation of NCX Variants: Updates and Challenges.International journal of molecular sciences · 2022Review
- Modulation of the cardiac NaCell calcium · 2020Review
- Key residues controlling bidirectional ion movements in NaCell calcium · 2018Article
- Molecular determinants of pH regulation in the cardiac NaThe Journal of general physiology · 2018Article
- Heparin Oligosaccharides Have Antiarrhythmic Effect by Accelerating the Sodium-Calcium Exchanger.Frontiers in cardiovascular medicine · 2018Article
- How a helix imposes palmitoylation of a membrane protein: What one can learn from NCX.The Journal of biological chemistry · 2017Article
- 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
- Structural Features of Ion Transport and Allosteric Regulation in Sodium-Calcium Exchanger (NCX) Proteins.Frontiers in physiology · 2016Review
- Palmitoylation of the Na/Ca exchanger cytoplasmic loop controls its inactivation and internalization during stress signaling.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2015Article
- Sodium-calcium exchangers (NCX): molecular hallmarks underlying the tissue-specific and systemic functions.Pflugers Archiv : European journal of physiology · 2014Review
- Population shift underlies Ca2+-induced regulatory transitions in the sodium-calcium exchanger (NCX).The Journal of biological chemistry · 2013Article
- NMR structure note: solution structure of Ca²⁺ binding domain 2B of the third isoform of the Na⁺/Ca²⁺ exchanger.Journal of biomolecular NMR · 2012Article
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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
Na(+)/Ca(2+) exchanger (NCX) proteins mediate Ca(2+)-fluxes across the cell membrane to maintain Ca(2+) homeostasis in many cell types. Eukaryotic NCX contains Ca(2+)-binding regulatory domains, CBD1 and CBD2. Ca(2+) binding to a primary sensor (Ca3-Ca4 sites) on CBD1 activates mammalian NCXs, whereas CALX, a Drosophila NCX ortholog, displays an inhibitory response to regulatory Ca(2+). To further elucidate the underlying regulatory mechanisms, we determined the 2.7 Å crystal structure of mammalian CBD12-E454K, a two-domain construct that retains wild-type properties. In conjunction with stopped-flow kinetics and SAXS (small-angle X-ray scattering) analyses of CBD12 mutants, we show that Ca(2+) binding to Ca3-Ca4 sites tethers the domains via a network of interdomain salt-bridges. This Ca(2+)-driven interdomain switch controls slow dissociation of "occluded" Ca(2+) from the primary sensor and thus dictates Ca(2+) sensing dynamics. In the Ca(2+)-bound conformation, the interdomain angle of CBD12 is very similar in NCX and CALX, meaning that the interdomain distances cannot account for regulatory diversity in NCX and CALX. Since the two-domain interface is nearly identical among eukaryotic NCXs, including CALX, we suggest that the Ca(2+)-driven interdomain switch described here represents a general mechanism for initial conduction of regulatory signals in NCX variants.
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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.