ArticleBiophysical journal2005
The alpha-helical propensity of the cytoplasmic domain of phospholamban: a molecular dynamics simulation of the effect of phosphorylation and mutation.
Article in Biophysical journal, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 44 citations in OpenAlex.
- Allosteric Modulation of SERCA Pumps in Health and Disease: Structural Dynamics, Posttranslational Modifications, and Therapeutic Potential.Journal of molecular biology · 2025Review
- Thirty years of molecular dynamics simulations on posttranslational modifications of proteins.Physical chemistry chemical physics : PCCP · 2022Review
- Molecular dynamics shows complex interplay and long-range effects of post-translational modifications in yeast protein interactions.PLoS computational biology · 2021Article
- Atomistic Structure and Dynamics of the CaInternational journal of molecular sciences · 2020Article
- Crystal structure of diamondback moth ryanodine receptor Repeat34 domain reveals insect-specific phosphorylation sites.BMC biology · 2019Article
- Structural basis for relief of phospholamban-mediated inhibition of the sarcoplasmic reticulum CaThe Journal of biological chemistry · 2018Article
- Perturbations of Native Membrane Protein Structure in Alkyl Phosphocholine Detergents: A Critical Assessment of NMR and Biophysical Studies.Chemical reviews · 2018Review
- Acute inotropic and lusitropic effects of cardiomyopathic R9C mutation of phospholamban.The Journal of biological chemistry · 2015Article
- 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
- Probing the interaction of Arg9Cys mutated phospholamban with phospholipid bilayers by solid-state NMR spectroscopy.Biochimica et biophysica acta · 2013Article
- Structural dynamics of muscle protein phosphorylation.Journal of muscle research and cell motility · 2012Review
- Lethal, hereditary mutants of phospholamban elude phosphorylation by protein kinase A.The Journal of biological chemistry · 2012Article
- Protein Electrostatic Properties Predefining the Level of Surface Hydrophobicity Change upon Phosphorylation.The journal of physical chemistry letters · 2012Article
- An acidic loop and cognate phosphorylation sites define a molecular switch that modulates ubiquitin charging activity in Cdc34-like enzymes.PLoS computational biology · 2011Article
- An allosteric mechanism inferred from molecular dynamics simulations on phospholamban pentamer in lipid membranes.PloS one · 2011Article
- Phosphorylation and mutation of phospholamban alter physical interactions with the sarcoplasmic reticulum calcium pump.Journal of molecular biology · 2011Article
- Phosphorylation-induced structural changes in smooth muscle myosin regulatory light chain.Proceedings of the National Academy of Sciences of the United States of America · 2010Article
- Effect of membrane thickness on conformational sampling of phospholamban from computer simulations.Biophysical journal · 2010Article
- Structure, dynamics, and ion conductance of the phospholamban pentamer.Biophysical journal · 2009Article
- Thermodynamic and structural basis of phosphorylation-induced disorder-to-order transition in the regulatory light chain of smooth muscle myosin.Journal of the American Chemical Society · 2008Article
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2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We have used molecular dynamics simulations to investigate the effect of phosphorylation and mutation on the cytoplasmic domain of phospholamban (PLB), a 52-residue protein that regulates the calcium pump in cardiac muscle. Simulations were carried out in explicit water systems at 300 K for three peptides spanning the first 25 residues of PLB: wild-type (PLB(1-25)), PLB(1-25) phosphorylated at Ser16 and PLB(1-25) with the R9C mutation, which is known to cause human heart disease. The unphosphorylated peptide maintains a helical conformation from 3 to 15 throughout a 26-ns simulation, in agreement with spectroscopic data. Comparison with simulations of a fourth peptide truncated at Pro21 showed the importance of the region from 17 to 21 in preventing local unfolding of the helix. The results suggest that residues 11-16 are more likely to unfold when specific capping motifs are not present. It is proposed that protein kinase A exploits the intrinsic flexibility of the 11-21 region when binding PLB. In agreement with available CD and NMR data, the simulations show a decrease in the helical content upon phosphorylation. The phosphorylated peptide is characterized by helix spanning residues 3-11, followed by a turn that optimizes the salt-bridge interaction between the side chains of the phosphorylated Ser-16 and Arg-13. Replacing Arg-9 with Cys results in unfolding of the helix from C9 and an overall decrease of the helical conformation. The simulations show that initiation of unfolding is due to increased solvent accessibility of the backbone atoms near the smaller Cys. It is proposed that the loss of inhibitory potency upon Ser-16 phosphorylation or R9C mutation of PLB is due to a similar mechanism, in which the partial unfolding of the cytoplasmic helix of PLB results in a conformation that interacts with the cytoplasmic domain of the calcium pump to relieve its inhibition.
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