ArticleProceedings of the National Academy of Sciences of the United States of America2007
The second Ca2+-binding domain of the Na+ Ca2+ exchanger is essential for regulation: crystal structures and mutational analysis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
56 citing papers in PubMed, 105 citations in OpenAlex.
- Article
- Probing Charge-Controlled Inter-Domain Flexibility: Integrating Experimental and Coarse-Grained Approaches.Journal of chemical information and modeling · 2026Article
- Druggability of Sodium Calcium Exchanger (NCX): Challenges and Recent Development.International journal of molecular sciences · 2025Review
- 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
- Association of polymorphisms of calcium reabsorption genes SLC12A1, KCNJ1 and SLC8A1 with colorectal adenoma.Journal of cancer research and clinical oncology · 2023Article
- Structure-Based Function and Regulation of NCX Variants: Updates and Challenges.International journal of molecular sciences · 2022Review
- Molecular insights on CALX-CBD12 interdomain dynamics from MD simulations, RDCs, and SAXS.Biophysical journal · 2021Article
- Insights into the molecular basis of the palmitoylation and depalmitoylation of NCX1.Cell calcium · 2021Article
- A guide to plasma membrane solute carrier proteins.The FEBS journal · 2021Review
- Sodium-Calcium Exchangers of the SLC8 Family in Oligodendrocytes: Functional Properties in Health and Disease.Neurochemical research · 2020Review
- Intracellular CaProceedings of the National Academy of Sciences of the United States of America · 2020Article
- Modulation of the cardiac NaCell calcium · 2020Review
- Regulation of Membrane Calcium Transport Proteins by the Surrounding Lipid Environment.Biomolecules · 2019Review
- CaProceedings of the National Academy of Sciences of the United States of America · 2019Article
- 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
- Interactions between calcium intake and polymorphisms in genes essential for calcium reabsorption and risk of colorectal neoplasia in a two-phase study.Molecular carcinogenesis · 2017Article
Corrections and comments
- Commented on by
Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
The Na(+)-Ca(2+) exchanger plays a central role in cardiac contractility by maintaining Ca(2+) homeostasis. Two Ca(2+)-binding domains, CBD1 and CBD2, located in a large intracellular loop, regulate activity of the exchanger. Ca(2+) binding to these regulatory domains activates the transport of Ca(2+) across the plasma membrane. Previously, we solved the structure of CBD1, revealing four Ca(2+) ions arranged in a tight planar cluster. Here, we present structures of CBD2 in the Ca(2+)-bound (1.7-A resolution) and -free (1.4-A resolution) conformations. Like CBD1, CBD2 has a classical Ig fold but coordinates only two Ca(2+) ions in primary and secondary Ca(2+) sites. In the absence of Ca(2+), Lys(585) stabilizes the structure by coordinating two acidic residues (Asp(552) and Glu(648)), one from each of the Ca(2+)-binding sites, and prevents a substantial protein unfolding. We have mutated all of the acidic residues that coordinate the Ca(2+) ions and have examined the effects of these mutations on regulation of exchange activity. Three mutations (E516L, D578V, and E648L) at the primary Ca(2+) site completely remove Ca(2+) regulation, placing the exchanger into a constitutively active state. These are the first data defining the role of CBD2 as a regulatory domain in the Na(+)-Ca(2+) exchanger.
Indexed as
Identifiers
What OpenQuestion holds
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.