ArticleNature2012
A bimodular mechanism of calcium control in eukaryotes.
Article in Nature, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
What it found
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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.
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Who cites it
49 citing papers in PubMed, 125 citations in OpenAlex.
- Functional Calmodulin States Are Selected from an Electrostatically Tuned Free Energy Landscape.Journal of chemical information and modeling · 2026Article
- Plasma membrane calcium ATPases and cerebellar pathology: what's the role in the ataxia?Biology direct · 2025Review
- An intracellular CPK-ECA1 phosphoregulatory circuit couples calcium signatures to ABA homeostasis for plant osmosensivity.Science advances · 2025Article
- Evolutionarily conserved BON1 regulates the basal cytosolic CaProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Phosphorylation of CAX transporters controls CaPlant communications · 2024Article
- Tubulin Regulates Plasma Membrane CaCell biochemistry and biophysics · 2024Review
- Hypothesis paper: the development of a regulatory layer in P2B autoinhibited CaPlant signaling & behavior · 2023Article
- Monomeric α-synuclein activates the plasma membrane calcium pump.The EMBO journal · 2023Article
- Resting cytosol Ca2+ level maintained by Ca2+ pumps affects environmental responses in Arabidopsis.Plant physiology · 2023Article
- Structures of calmodulin-melittin complexes show multiple binding modes lacking classical anchoring interactions.The Journal of biological chemistry · 2023Article
- Linalool Activates Oxidative and Calcium Burst and CAM3-ACA8 Participates in Calcium Recovery in Arabidopsis Leaves.International journal of molecular sciences · 2022Article
- Structure, Function and Regulation of the Plasma Membrane Calcium Pump in Health and Disease.International journal of molecular sciences · 2022Review
- Proton and calcium pumping P-type ATPases and their regulation of plant responses to the environment.Plant physiology · 2021Review
- Calmodulin7: recent insights into emerging roles in plant development and stress.Plant molecular biology · 2021Review
- Separation of presynaptic CaProceedings of the National Academy of Sciences of the United States of America · 2021Article
- Membrane Transport Proteins in Osteoclasts: The Ins and Outs.Frontiers in cell and developmental biology · 2021Review
- Analysis of Arabidopsis TPK2 and KCO3 reveals structural properties required for KChannels (Austin, Tex.) · 2020Article
- Primary Active CaCold Spring Harbor perspectives in biology · 2020Review
- Novel CaM-binding motif in its NudT9H domain contributes to temperature sensitivity of TRPM2.Biochimica et biophysica acta. Molecular cell research · 2019Article
- Structure of the human plasma membrane CaNature communications · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 4 institutions in 3 countries.
Funding
Abstract
Calcium ions (Ca(2+)) have an important role as secondary messengers in numerous signal transduction processes, and cells invest much energy in controlling and maintaining a steep gradient between intracellular (∼0.1-micromolar) and extracellular (∼2-millimolar) Ca(2+) concentrations. Calmodulin-stimulated calcium pumps, which include the plasma-membrane Ca(2+)-ATPases (PMCAs), are key regulators of intracellular Ca(2+) in eukaryotes. They contain a unique amino- or carboxy-terminal regulatory domain responsible for autoinhibition, and binding of calcium-loaded calmodulin to this domain releases autoinhibition and activates the pump. However, the structural basis for the activation mechanism is unknown and a key remaining question is how calmodulin-mediated PMCA regulation can cover both basal Ca(2+) levels in the nanomolar range as well as micromolar-range Ca(2+) transients generated by cell stimulation. Here we present an integrated study combining the determination of the high-resolution crystal structure of a PMCA regulatory-domain/calmodulin complex with in vivo characterization and biochemical, biophysical and bioinformatics data that provide mechanistic insights into a two-step PMCA activation mechanism mediated by calcium-loaded calmodulin. The structure shows the entire PMCA regulatory domain and reveals an unexpected 2:1 stoichiometry with two calcium-loaded calmodulin molecules binding to different sites on a long helix. A multifaceted characterization of the role of both sites leads to a general structural model for calmodulin-mediated regulation of PMCAs that allows stringent, highly responsive control of intracellular calcium in eukaryotes, making it possible to maintain a stable, basal level at a threshold Ca(2+) concentration, where steep activation occurs.
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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.