ArticleProceedings of the National Academy of Sciences of the United States of America2013
Allosteric regulation of SERCA by phosphorylation-mediated conformational shift of phospholamban.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers.
What it found
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Who cites it
84 citing papers in PubMed, 137 citations in OpenAlex.
- Sarcolipin is a Conformation-Dependent Regulator of the Sarcoplasmic Reticulum Calcium Pump SERCA.The Journal of membrane biology · 2026Article
- No Time to Fold: Intrinsically Disordered Microproteins in Action.Biochemistry · 2026Review
- Nuclear magnetic resonance of membrane proteins-Advances and opportunities.Current opinion in structural biology · 2026Review
- Phosphodiesterase 8 regulation of excitation-contraction coupling as a target for cardiovascular disease: is it my turn now?American journal of physiology. Heart and circulatory physiology · 2026Review
- Investigating PKD2 deficiency-associated cardiomyopathies using hESC-cardiomyocytes and bioengineered 3D ventricular cardiac tissue strips.Cell death & disease · 2026Article
- Allosteric Modulation of SERCA Pumps in Health and Disease: Structural Dynamics, Posttranslational Modifications, and Therapeutic Potential.Journal of molecular biology · 2025Review
- PAD2 disturbs cardiomyocyte calcium homeostasis by citrullinating SERCA2a protein in hemorrhagic shock induced arrhythmia.The journal of trauma and acute care surgery · 2025Article
- A retinoic acid:YAP1 signaling axis controls atrial lineage commitment.Cell reports · 2025Article
- Review
- Genetic landscape of phospholamban cardiomyopathies.Frontiers in cell and developmental biology · 2025Review
- Dipolar Recoupling in Rotating Solids.Chemical reviews · 2024Review
- Pathological mutations in the phospholamban cytoplasmic region affect its topology and dynamics modulating the extent of SERCA inhibition.Biochimica et biophysica acta. Biomembranes · 2024Article
- Article
- Phospholamban pentamerization increases sensitivity and dynamic range of cardiac relaxation.Cardiovascular research · 2023Article
- Cadmium exposure induces a sex-dependent decline in left ventricular cardiac function.Life sciences · 2023Article
- PHRONESIS: A One-Shot Approach for Sequential Assignment of Protein Resonances by Ultrafast MAS Solid-State NMR Spectroscopy.Chemphyschem : a European journal of chemical physics and physical chemistry · 2022Article
- Blocking phospholamban with VHH intrabodies enhances contractility and relaxation in heart failure.Nature communications · 2022Article
- Article
- Regulation of ER-derived membrane dynamics by the DedA domain-containing proteins VMP1 and TMEM41B.EMBO reports · 2022Review
- The effects of neurogranin knockdown on SERCA pump efficiency in soleus muscles of female mice fed a high fat diet.Frontiers in endocrinology · 2022Article
24 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
The membrane protein complex between the sarcoplasmic reticulum Ca(2+)-ATPase (SERCA) and phospholamban (PLN) controls Ca(2+) transport in cardiomyocytes, thereby modulating cardiac contractility. β-Adrenergic-stimulated phosphorylation of PLN at Ser-16 enhances SERCA activity via an unknown mechanism. Using solid-state nuclear magnetic resonance spectroscopy, we mapped the physical interactions between SERCA and both unphosphorylated and phosphorylated PLN in membrane bilayers. We found that the allosteric regulation of SERCA depends on the conformational equilibrium of PLN, whose cytoplasmic regulatory domain interconverts between three different states: a ground T state (helical and membrane associated), an excited R state (unfolded and membrane detached), and a B state (extended and enzyme-bound), which is noninhibitory. Phosphorylation at Ser-16 of PLN shifts the populations toward the B state, increasing SERCA activity. We conclude that PLN's conformational equilibrium is central to maintain SERCA's apparent Ca(2+) affinity within a physiological window. This model represents a paradigm shift in our understanding of SERCA regulation by posttranslational phosphorylation and suggests strategies for designing innovative therapeutic approaches to enhance cardiac muscle contractility.
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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.