ArticleJournal of muscle research and cell motility2012
Tuning the structural coupling between the transmembrane and cytoplasmic domains of phospholamban to control sarcoplasmic reticulum Ca(2+)-ATPase (SERCA) function.
Article in Journal of muscle research and cell motility, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 23 citations in OpenAlex.
- A novel transdermal curcumin gel shows potential in improving cardiac bioenergetic functions in Berkeley sickle cell mice.Blood vessels, thrombosis & hemostasis · 2026Article
- Pathological mutations in the phospholamban cytoplasmic region affect its topology and dynamics modulating the extent of SERCA inhibition.Biochimica et biophysica acta. Biomembranes · 2024Article
- Proton-detected polarization optimized experiments (POE) using ultrafast magic angle spinning solid-state NMR: Multi-acquisition of membrane protein spectra.Journal of magnetic resonance (San Diego, Calif. : 1997) · 2020Article
- Intrinsically disordered HAX-1 regulates CaBiochimica et biophysica acta. Biomembranes · 2020Article
- Probing membrane protein ground and conformationally excited states using dipolar- and J-coupling mediated MAS solid state NMR experiments.Methods (San Diego, Calif.) · 2018Review
- Effects of the Arg9Cys and Arg25Cys mutations on phospholamban's conformational equilibrium in membrane bilayers.Biochimica et biophysica acta. Biomembranes · 2018Article
- Perturbations of Native Membrane Protein Structure in Alkyl Phosphocholine Detergents: A Critical Assessment of NMR and Biophysical Studies.Chemical reviews · 2018Review
- Article
- Reversal of Phospholamban Inhibition of the Sarco(endo)plasmic Reticulum Ca2+-ATPase (SERCA) Using Short, Protein-interacting RNAs and Oligonucleotide Analogs.The Journal of biological chemistry · 2016Article
- Accurate Determination of Conformational Transitions in Oligomeric Membrane Proteins.Scientific reports · 2016Article
- Rheostatic Regulation of the SERCA/Phospholamban Membrane Protein Complex Using Non-Coding RNA and Single-Stranded DNA oligonucleotides.Scientific reports · 2015Article
- Phospholamban phosphorylation, mutation, and structural dynamics: a biophysical approach to understanding and treating cardiomyopathy.Biophysical reviews · 2015Article
- Effects of naturally occurring arginine 14 deletion on phospholamban conformational dynamics and membrane interactions.Biochimica et biophysica acta · 2015Article
- Structural dynamics and conformational equilibria of SERCA regulatory proteins in membranes by solid-state NMR restrained simulations.Biophysical journal · 2014Article
- Structural dynamics and topology of phosphorylated phospholamban homopentamer reveal its role in the regulation of calcium transport.Structure (London, England : 1993) · 2013Article
- Allosteric regulation of SERCA by phosphorylation-mediated conformational shift of phospholamban.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Structures of the excited states of phospholamban and shifts in their populations upon phosphorylation.Biochemistry · 2013Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Phospholamban (PLN) is the endogenous inhibitor of the sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA), the integral membrane enzyme responsible for 70 % of the removal of Ca(2+) from the cytosol, inducing cardiac muscle relaxation in humans. Dysfunctions in SERCA:PLN interactions have been implicated as having a critical role in cardiac disease, and targeting Ca(2+) transport has been demonstrated to be a promising avenue in treating conditions of heart failure. Here, we designed a series of new mutants able to tune SERCA function, targeting the loop sequence that connects the transmembrane and cytoplasmic helices of PLN. We found that a variable degree of loss of inhibition mutants is attainable by engineering glycine mutations along PLN's loop domain. Remarkably, a double glycine mutation results in a complete loss-of-function mutant, fully mimicking the phosphorylated state of PLN. Using nuclear magnetic resonance spectroscopy, we rationalized the effects of these mutations in terms of entropic control on PLN function, whose inhibitory function can be modulated by increasing its conformational dynamics. However, if PLN mutations go past a threshold set by the phosphorylated state, they break the structural coupling between the transmembrane and cytoplasmic domains, resulting in a species that behaves as the inhibitory transmembrane domain alone. These studies provide new potential candidates for gene therapy to reverse the effects of heart failure.
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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.