ArticleThe Journal of biological chemistry2013
Population shift underlies Ca2+-induced regulatory transitions in the sodium-calcium exchanger (NCX).
Article in The Journal of biological chemistry, 2013. 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.
- Article
- The NaThe Journal of veterinary medical science · 2026Review
- Use of biomolecular emulator for characterizing flexible proteins by small-angle x-ray scattering.Protein science : a publication of the Protein Society · 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 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
- Sodium-Calcium Exchangers of the SLC8 Family in Oligodendrocytes: Functional Properties in Health and Disease.Neurochemical research · 2020Review
- Modulation of the cardiac NaCell calcium · 2020Review
- Key residues controlling bidirectional ion movements in NaCell calcium · 2018Article
- Structure-based dynamic arrays in regulatory domains of sodium-calcium exchanger (NCX) isoforms.Scientific reports · 2017Article
- Modeling NaJournal of molecular and cellular cardiology · 2016Article
- Asymmetric Preorganization of Inverted Pair Residues in the Sodium-Calcium Exchanger.Scientific reports · 2016Article
- Structural Features of Ion Transport and Allosteric Regulation in Sodium-Calcium Exchanger (NCX) Proteins.Frontiers in physiology · 2016Review
- Sodium recognition by the Na+/Ca2+ exchanger in the outward-facing conformation.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Sodium-calcium exchangers (NCX): molecular hallmarks underlying the tissue-specific and systemic functions.Pflugers Archiv : European journal of physiology · 2014Review
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4 authors.
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Abstract
In eukaryotic Na(+)/Ca(2+) exchangers (NCX) the Ca(2+) binding CBD1 and CBD2 domains form a two-domain regulatory tandem (CBD12). An allosteric Ca(2+) sensor (Ca3-Ca4 sites) is located on CBD1, whereas CBD2 contains a splice-variant segment. Recently, a Ca(2+)-driven interdomain switch has been described, albeit how it couples Ca(2+) binding with signal propagation remains unclear. To resolve the dynamic features of Ca(2+)-induced conformational transitions we analyze here distinct splice variants and mutants of isolated CBD12 at varying temperatures by using small angle x-ray scattering (SAXS) and equilibrium (45)Ca(2+) binding assays. The ensemble optimization method SAXS analysis demonstrates that the apo and Mg(2+)-bound forms of CBD12 are highly flexible, whereas Ca(2+) binding to the Ca3-Ca4 sites results in a population shift of conformational landscape to more rigidified states. Population shift occurs even under conditions in which no effect of Ca(2+) is observed on the globally derived Dmax (maximal interatomic distance), although under comparable conditions a normal [Ca(2+)]-dependent allosteric regulation occurs. Low affinity sites (Ca1-Ca2) of CBD1 do not contribute to Ca(2+)-induced population shift, but the occupancy of these sites by 1 mM Mg(2+) shifts the Ca(2+) affinity (Kd) at the neighboring Ca3-Ca4 sites from ∼ 50 nM to ∼ 200 nM and thus, keeps the primary Ca(2+) sensor (Ca3-Ca4 sites) within a physiological range. Thus, Ca(2+) binding to the Ca3-Ca4 sites results in a population shift, where more constraint conformational states become highly populated at dynamic equilibrium in the absence of global conformational transitions in CBD alignment.
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