ArticleProceedings of the National Academy of Sciences of the United States of America2009
Structural basis for the high Ca2+ affinity of the ubiquitous SERCA2b Ca2+ pump.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 85 citations in OpenAlex.
- Mitochondria-ER crosstalk via MAMS: Bridging cellular homeostasis and cancer progression.Apoptosis : an international journal on programmed cell death · 2026Review
- The SERCA Pump: A Key Molecular Target in Calcium Handling of Vascular Smooth Muscle Cells in Metabolic Syndrome.Handbook of experimental pharmacology · 2026Review
- Allosteric Modulation of SERCA Pumps in Health and Disease: Structural Dynamics, Posttranslational Modifications, and Therapeutic Potential.Journal of molecular biology · 2025Review
- Identification of a molecular resistor that controls UCP1-independent CaCell metabolism · 2025Article
- Linking Circadian Rhythms to Gut-Brain Axis Lipid Metabolism Associated With Endoplasmic Reticulum Stress in Alzheimer's Disease.CNS neuroscience & therapeutics · 2025Review
- The correlation between mitochondria-associated endoplasmic reticulum membranes (MAMs) and CaActa pharmacologica Sinica · 2025Review
- Endoplasmic reticulum stress in abdominal aortic aneurysm.International journal of cardiology. Heart & vasculature · 2024Review
- Darier disease is associated with neurodegenerative disorders and epilepsy.Scientific reports · 2024Article
- Involvement of nucleus accumbens SERCA2b in methamphetamine-induced conditioned place preference.Addiction biology · 2024Article
- The Meeting of Micropeptides with Major CaMembranes · 2023Review
- Arc ubiquitination regulates endoplasmic reticulum-mediated CaFrontiers in cellular neuroscience · 2023Article
- Advances in Intracellular Calcium Signaling Reveal Untapped Targets for Cancer Therapy.Biomedicines · 2021Review
- Nothing Regular about the Regulins: Distinct Functional Properties of SERCA Transmembrane Peptide Regulatory Subunits.International journal of molecular sciences · 2021Review
- Patients with Darier Disease Exhibit Cognitive Impairment while Patients with Hailey-Hailey Disease Do Not: An Experimental, Matched Case-control Study.Acta dermato-venereologica · 2021Article
- Darier Disease - A Multi-organ Condition?Acta dermato-venereologica · 2021Review
- Presynaptic endoplasmic reticulum regulates short-term plasticity in hippocampal synapses.Communications biology · 2021Article
- Chronic but not acute pharmacological activation of SERCA induces behavioral and neurochemical effects in male and female mice.Behavioural brain research · 2021Article
- Cryo-EM structures of SERCA2b reveal the mechanism of regulation by the luminal extension tail.Science advances · 2020Article
- Lessons from the Endoplasmic Reticulum CaCells · 2020Review
- Linking Biochemical and Structural States of SERCA: Achievements, Challenges, and New Opportunities.International journal of molecular sciences · 2020Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sarco(endo)plasmic reticulum Ca(2+) ATPase (SERCA) Ca(2+) transporters pump cytosolic Ca(2+) into the endoplasmic reticulum, maintaining a Ca(2+) gradient that controls vital cell functions ranging from proliferation to death. To meet the physiological demand of the cell, SERCA activity is regulated by adjusting the affinity for Ca(2+) ions. Of all SERCA isoforms, the housekeeping SERCA2b isoform displays the highest Ca(2+) affinity because of a unique C-terminal extension (2b-tail). Here, an extensive structure-function analysis of SERCA2b mutants and SERCA1a2b chimera revealed how the 2b-tail controls Ca(2+) affinity. Its transmembrane (TM) segment (TM11) and luminal extension functionally cooperate and interact with TM7/TM10 and luminal loops of SERCA2b, respectively. This stabilizes the Ca(2+)-bound E1 conformation and alters Ca(2+)-transport kinetics, which provides the rationale for the higher apparent Ca(2+) affinity. Based on our NMR structure of TM11 and guided by mutagenesis results, a structural model was developed for SERCA2b that supports the proposed 2b-tail mechanism and is reminiscent of the interaction between the alpha- and beta-subunits of Na(+),K(+)-ATPase. The 2b-tail interaction site may represent a novel target to increase the Ca(2+) affinity of malfunctioning SERCA2a in the failing heart to improve contractility.
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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.