ArticleBiophysical journal2013
Phosphorylated phospholamban stabilizes a compact conformation of the cardiac calcium-ATPase.
Article in Biophysical journal, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 50 citations in OpenAlex.
- Fluorescence Lifetime Spectroscopy Reveals Distinct Allosteric Mechanisms of SERCA Inhibitors.The Journal of membrane biology · 2026Article
- Allosteric Modulation of SERCA Pumps in Health and Disease: Structural Dynamics, Posttranslational Modifications, and Therapeutic Potential.Journal of molecular biology · 2025Review
- Mechanisms for cardiac calcium pump activation by its substrate and a synthetic allosteric modulator using fluorescence lifetime imaging.PNAS nexus · 2024Article
- Fluorescence lifetime FRET assay for live-cell high-throughput screening of the cardiac SERCA pump yields multiple classes of small-molecule allosteric modulators.Scientific reports · 2023Article
- FRET assay for live-cell high-throughput screening of the cardiac SERCA pump yields multiple classes of small-molecule allosteric modulators.Research square · 2023Article
- Fluorescence lifetime imaging microscopy reveals sodium pump dimers in live cells.The Journal of biological chemistry · 2022Article
- Ranolazine rescues the heart failure phenotype of PLN-deficient human pluripotent stem cell-derived cardiomyocytes.Stem cell reports · 2022Article
- Cardiac calcium regulation in human induced pluripotent stem cell cardiomyocytes: Implications for disease modeling and maturation.Frontiers in cell and developmental biology · 2022Review
- Dynamics-Driven Allostery Underlies CaBiophysical journal · 2020Article
- Atomistic Structure and Dynamics of the CaInternational journal of molecular sciences · 2020Article
- Protein docking and steered molecular dynamics suggest alternative phospholamban-binding sites on the SERCA calcium transporter.The Journal of biological chemistry · 2020Article
- Linking Biochemical and Structural States of SERCA: Achievements, Challenges, and New Opportunities.International journal of molecular sciences · 2020Review
- A hallmark of phospholamban functional divergence is located in the N-terminal phosphorylation domain.Computational and structural biotechnology journal · 2020Article
- Viral expression of a SERCA2a-activating PLB mutant improves calcium cycling and synchronicity in dilated cardiomyopathic hiPSC-CMs.Journal of molecular and cellular cardiology · 2020Article
- Probing the effects of nonannular lipid binding on the stability of the calcium pump SERCA.Scientific reports · 2019Article
- Article
- Development of Novel Intramolecular FRET-Based ABC Transporter Biosensors to Identify New Substrates and Modulators.Pharmaceutics · 2018Article
- Targeting protein-protein interactions for therapeutic discovery via FRET-based high-throughput screening in living cells.Scientific reports · 2018Article
- Redistribution of SERCA calcium pump conformers during intracellular calcium signaling.The Journal of biological chemistry · 2018Article
- Effects of the Arg9Cys and Arg25Cys mutations on phospholamban's conformational equilibrium in membrane bilayers.Biochimica et biophysica acta. Biomembranes · 2018Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
The sarcoendoplasmic reticulum calcium ATPase (SERCA) plays a key role in cardiac calcium handling and is considered a high-value target for the treatment of heart failure. SERCA undergoes conformational changes as it harnesses the chemical energy of ATP for active transport. X-ray crystallography has provided insight into SERCA structural substates, but it is not known how well these static snapshots describe in vivo conformational dynamics. The goals of this work were to quantify the direction and magnitude of SERCA motions as the pump performs work in live cardiac myocytes, and to identify structural determinants of SERCA regulation by phospholamban. We measured intramolecular fluorescence resonance energy transfer (FRET) between fluorescent proteins fused to SERCA cytoplasmic domains. We detected four discrete structural substates for SERCA expressed in cardiac muscle cells. The relative populations of these discrete states oscillated with electrical pacing. Low FRET states were most populated in low Ca (diastole), and were indicative of an open, disordered structure for SERCA in the E2 (Ca-free) enzymatic substate. High FRET states increased with Ca (systole), suggesting rigidly closed conformations for the E1 (Ca-bound) enzymatic substates. Notably, a special compact E1 state was observed after treatment with β-adrenergic agonist or with coexpression of phosphomimetic mutants of phospholamban. The data suggest that SERCA calcium binding induces the pump to undergo a transition from an open, dynamic conformation to a closed, ordered structure. Phosphorylated phospholamban stabilizes a unique conformation of SERCA that is characterized by a compact architecture.
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