ArticleBiochemistry2011
Activating and deactivating roles of lipid bilayers on the Ca(2+)-ATPase/phospholamban complex.
Article in Biochemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 71 citations in OpenAlex.
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- Allosteric Modulation of SERCA Pumps in Health and Disease: Structural Dynamics, Posttranslational Modifications, and Therapeutic Potential.Journal of molecular biology · 2025Review
- Glycerophospholipids in ALS: insights into disease mechanisms and clinical implication.Molecular neurodegeneration · 2025Review
- Paradoxical SERCA2a Dysregulation Contributes to Atrial Fibrillation in a Model of Diet-Induced Obesity.International journal of molecular sciences · 2025Article
- Machine Learning-Driven Discovery of Structurally Related Natural Products as Activators of the Cardiac Calcium Pump SERCA2a.ChemMedChem · 2025Article
- Housing Temperature Impacts the Systemic and Tissue-Specific Molecular Responses to Cancer in Mice.Journal of cachexia, sarcopenia and muscle · 2025Article
- Linking Circadian Rhythms to Gut-Brain Axis Lipid Metabolism Associated With Endoplasmic Reticulum Stress in Alzheimer's Disease.CNS neuroscience & therapeutics · 2025Review
- Calcium Handling in Inherited Cardiac Diseases: A Focus on Catecholaminergic Polymorphic Ventricular Tachycardia and Hypertrophic Cardiomyopathy.International journal of molecular sciences · 2023Review
- Electrostatic interactions between single arginine and phospholipids modulate physiological properties of sarcoplasmic reticulum CaScientific reports · 2022Article
- Structural basis for sarcolipin's regulation of muscle thermogenesis by the sarcoplasmic reticulum CaScience advances · 2021Article
- The role of sigma 1 receptor in organization of endoplasmic reticulum signaling microdomains.eLife · 2021Article
- Sigma-1 Receptor (S1R) Interaction with Cholesterol: Mechanisms of S1R Activation and Its Role in Neurodegenerative Diseases.International journal of molecular sciences · 2021Article
- Linking Biochemical and Structural States of SERCA: Achievements, Challenges, and New Opportunities.International journal of molecular sciences · 2020Review
- Intrinsically disordered HAX-1 regulates CaBiochimica et biophysica acta. Biomembranes · 2020Article
- Regulation of Membrane Calcium Transport Proteins by the Surrounding Lipid Environment.Biomolecules · 2019Review
- General and specific interactions of the phospholipid bilayer with P-type ATPases.Biophysical reviews · 2019Review
- Significance of bilayer-forming phospholipids for skeletal muscle insulin sensitivity and mitochondrial function.Journal of biomedical research · 2019Article
- Emerging Diversity in Lipid-Protein Interactions.Chemical reviews · 2019Review
- The Fluidity of Phosphocholine and Maltoside Micelles and the Effect of CHAPS.Biophysical journal · 2019Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The physicochemical properties of the lipid bilayer shape the structure and topology of membrane proteins and regulate their biological function. Here, we investigated the functional effects of various lipid bilayer compositions on the sarcoplasmic reticulum (SR) Ca(2+)-ATPase (SERCA) in the presence and absence of its endogenous regulator, phospholamban (PLN). In the cardiac muscle, SERCA hydrolyzes one ATP molecule to translocate two Ca(2+) ions into the SR membrane per enzymatic cycle. Unphosphorylated PLN reduces SERCA's affinity for Ca(2+) and affects the enzymatic turnover. We varied bilayer thickness, headgroup, and fluidity and found that both the maximal velocity (V(max)) of the enzyme and its apparent affinity for Ca(2+) (K(Ca)) are strongly affected. Our results show that (a) SERCA's V(max) has a biphasic dependence on bilayer thickness, reaching maximum activity with 22-carbon lipid chain length, (b) phosphatidylethanolamine (PE) and phosphatidylserine (PS) increase Ca(2+) affinity, and (c) monounsaturated lipids afford higher SERCA V(max) and Ca(2+) affinity than diunsaturated lipids. The presence of PLN removes the activating effect of PE and shifts SERCA's activity profile, with a maximal activity reached in bilayers with 20-carbon lipid chain length. Our results in synthetic lipid systems compare well with those carried out in native SR lipids. Importantly, we found that specific membrane compositions closely reproduce PLN effects (V(max) and K(Ca)) found in living cells, reconciling an ongoing controversy regarding the regulatory role of PLN on SERCA function. Taken with the physiological changes occurring in the SR membrane composition, these studies underscore a possible allosteric role of the lipid bilayers on the SERCA/PLN complex.
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Registered trials
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