ArticleJournal of molecular biology2012
Structural and functional dynamics of an integral membrane protein complex modulated by lipid headgroup charge.
Article in Journal of molecular biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 47 citations in OpenAlex.
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- Linking Circadian Rhythms to Gut-Brain Axis Lipid Metabolism Associated With Endoplasmic Reticulum Stress in Alzheimer's Disease.CNS neuroscience & therapeutics · 2025Review
- A Large-Scale High-Throughput Screen for Modulators of SERCA Activity.Biomolecules · 2022Article
- Sarcolipin Exhibits Abundant RNA Transcription and Minimal Protein Expression in Horse Gluteal Muscle.Veterinary sciences · 2020Article
- The Structural and Functional Diversity of Intrinsically Disordered Regions in Transmembrane Proteins.The Journal of membrane biology · 2019Review
- Probing the effects of nonannular lipid binding on the stability of the calcium pump SERCA.Scientific reports · 2019Article
- 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
- Effects of the Arg9Cys and Arg25Cys mutations on phospholamban's conformational equilibrium in membrane bilayers.Biochimica et biophysica acta. Biomembranes · 2018Article
- Structural Impact of Phosphorylation and Dielectric Constant Variation on Synaptotagmin's IDR.Biophysical journal · 2018Article
- Conformational memory in the association of the transmembrane protein phospholamban with the sarcoplasmic reticulum calcium pump SERCA.The Journal of biological chemistry · 2017Article
- Article
- Functions of intrinsic disorder in transmembrane proteins.Cellular and molecular life sciences : CMLS · 2017Review
- A Cardiomyopathy Mutation in the Myosin Essential Light Chain Alters Actomyosin Structure.Biophysical journal · 2017Article
- Extension of the Highly Mobile Membrane Mimetic to Transmembrane Systems through Customized in Silico Solvents.The journal of physical chemistry. B · 2017Article
- 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
- Spectral Unmixing Plate Reader: High-Throughput, High-Precision FRET Assays in Living Cells.SLAS discovery : advancing life sciences R & D · 2017Article
- Direct detection of SERCA calcium transport and small-molecule inhibition in giant unilamellar vesicles.Biochemical and biophysical research communications · 2016Article
- Site-directed spectroscopy of cardiac myosin-binding protein C reveals effects of phosphorylation on protein structural dynamics.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- A bifunctional spin label reports the structural topology of phospholamban in magnetically-aligned bicelles.Journal of magnetic resonance (San Diego, Calif. : 1997) · 2016Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
We have used membrane surface charge to modulate the structural dynamics of an integral membrane protein, phospholamban (PLB), and thereby its functional inhibition of the sarcoplasmic reticulum Ca-ATPase (SERCA). It was previously shown by electron paramagnetic resonance, in vesicles of neutral lipids, that the PLB cytoplasmic domain is in equilibrium between an ordered T state and a dynamically disordered R state and that phosphorylation of PLB increases the R state and relieves SERCA inhibition, suggesting that R is less inhibitory. Here, we sought to control the T/R equilibrium by an alternative means-varying the lipid headgroup charge, thus perturbing the electrostatic interaction of PLB's cationic cytoplasmic domain with the membrane surface. We resolved the T and R states not only by electron paramagnetic resonance in the absence of SERCA but also by time-resolved fluorescence resonance energy transfer from SERCA to PLB, thus probing directly the SERCA-PLB complex. Compared to neutral lipids, anionic lipids increased both the T population and SERCA inhibition, while cationic lipids had the opposite effects. In contrast to conventional models, decreased inhibition was not accompanied by decreased binding. We conclude that PLB binds to SERCA in two distinct structural states of the cytoplasmic domain: an inhibitory T state that interacts strongly with the membrane surface and a less inhibitory R state that interacts more strongly with the anionic SERCA cytoplasmic domain. Modulating membrane surface charge provides an effective way of investigating the correlation between structural dynamics and function of integral membrane proteins.
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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.