ArticleBiochemical and biophysical research communications2012
Phospholamban mutants compete with wild type for SERCA binding in living cells.
Article in Biochemical and biophysical research communications, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 32 citations in OpenAlex.
- PLN-L31A/I40A for the treatment of inherited heart disease caused by PLN-R14del mutations.Acta pharmacologica Sinica · 2026Article
- Efficacy of the New Inotropic Agent Istaroxime in Acute Heart Failure.Journal of clinical medicine · 2022Review
- Cardiac calcium regulation in human induced pluripotent stem cell cardiomyocytes: Implications for disease modeling and maturation.Frontiers in cell and developmental biology · 2022Review
- Targeting protein-protein interactions for therapeutic discovery via FRET-based high-throughput screening in living cells.Scientific reports · 2018Article
- Effect of Phosphorylation on Interactions between Transmembrane Domains of SERCA and Phospholamban.Biophysical journal · 2018Article
- High-Throughput Spectral and Lifetime-Based FRET Screening in Living Cells to Identify Small-Molecule Effectors of SERCA.SLAS discovery : advancing life sciences R & D · 2017Article
- ATP-Binding Cassette Transporter Structure Changes Detected by Intramolecular Fluorescence Energy Transfer for High-Throughput Screening.Molecular pharmacology · 2015Article
- Phospholamban phosphorylation, mutation, and structural dynamics: a biophysical approach to understanding and treating cardiomyopathy.Biophysical reviews · 2015Article
- Synthetic phosphopeptides enable quantitation of the content and function of the four phosphorylation states of phospholamban in cardiac muscle.The Journal of biological chemistry · 2014Article
- Time-resolved FRET reveals the structural mechanism of SERCA-PLB regulation.Biochemical and biophysical research communications · 2014Article
- Secondary structure, backbone dynamics, and structural topology of phospholamban and its phosphorylated and Arg9Cys-mutated forms in phospholipid bilayers utilizing 13C and 15N solid-state NMR spectroscopy.The journal of physical chemistry. B · 2014Article
- Discovery of enzyme modulators via high-throughput time-resolved FRET in living cells.Journal of biomolecular screening · 2014Article
- Comparison of the structure and function of phospholamban and the arginine-14 deficient mutant associated with dilated cardiomyopathy.PloS one · 2014Article
- Probing the interaction of Arg9Cys mutated phospholamban with phospholipid bilayers by solid-state NMR spectroscopy.Biochimica et biophysica acta · 2013Article
- Phosphorylated phospholamban stabilizes a compact conformation of the cardiac calcium-ATPase.Biophysical journal · 2013Article
- High-throughput FRET assay yields allosteric SERCA activators.Journal of biomolecular screening · 2013Article
- Structural dynamics of muscle protein phosphorylation.Journal of muscle research and cell motility · 2012Review
- Protein-protein interactions in calcium transport regulation probed by saturation transfer electron paramagnetic resonance.Biophysical journal · 2012Article
- 2-Color calcium pump reveals closure of the cytoplasmic headpiece with calcium binding.PloS one · 2012Article
- The transmembrane peptide DWORF activates SERCA2a via dual mechanisms.The Journal of biological chemistryArticle
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
We have used fluorescent fusion proteins stably expressed in HEK cells to detect directly the interaction between the sarcoplasmic reticulum Ca-ATPase (SERCA) and phospholamban (PLB) in living cells, in order to design PLB mutants for gene therapy. Ca(2+) cycling in muscle cells depends strongly on SERCA. Heart failure (HF), which contributes to 12% of US deaths, typically exhibits decreased SERCA activity, and several potential therapies for HF aim to increase SERCA activity. We are investigating the use of LOF-PLB mutants (PLB(M)) as gene therapy vectors to increase SERCA activity. Active SERCA1a and WT-PLB, tagged at their N termini with fluorescent proteins (CFP and YFP), were coexpressed in stable HEK cell lines, and fluorescence resonance energy transfer (FRET) was used to detect their interaction directly. Phosphorylation of PLB, induced by forskolin, caused an increase in FRET from CFP-SERCA to YFP-PLB, indicating that SERCA inhibition can be relieved without dissociation of the complex. This suggests that a LOF mutant might bind to SERCA with sufficient affinity to complete effectively with WT-PLB, thus relieving SERCA inhibition. Therefore, we transiently expressed a series of PLB(M) in the CFP-SERCA/YFP-PLB cell line, and found decreased FRET, implying competition between PLB(M) and WT-PLB for binding to SERCA. These results establish this FRET assay as a rapid and quantitative means of screening PLB(M) for optimization of gene therapy to activate SERCA, as needed for gene therapy in HF.
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