title: Structural dynamics and topology of phosphorylated phospholamban homopentamer reveal its role in the regulation of calcium transport.
abstract: Phospholamban (PLN) inhibits the sarco(endo)plasmic reticulum Ca²⁺-ATPase (SERCA), thereby regulating cardiac diastole. In membranes, PLN assembles into homopentamers that in both the phosphorylated and nonphosphorylated states have been proposed to form ion-selective channels. Here, we determined the structure of the phosphorylated pentamer using a combination of solution and solid-state nuclear magnetic resonance methods. We found that the pinwheel architecture of the homopentamer is preserved upon phosphorylation, with each monomer having an L-shaped conformation. The TM domains form a hydrophobic pore approximately 24 Å long and 2 Å in diameter, which is inconsistent with canonical Ca²⁺-selective channels. Phosphorylation, however, enhances the conformational dynamics of the cytoplasmic region of PLN, causing partial unwinding of the amphipathic helix. We propose that PLN oligomers act as storage for active monomers, keeping SERCA function within a physiological window.
authors.affiliation: Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Vitaly V
authors.initials: VV
authors.lastname: Vostrikov
authors.forename: Kaustubh R
authors.initials: KR
authors.lastname: Mote
authors.forename: Raffaello
authors.initials: R
authors.lastname: Verardi
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Veglia
mesh_terms: D002118:Calcium / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000737:chemistry*; D017136:Ion Transport; D056004:Molecular Dynamics Simulation; D019906:Nuclear Magnetic Resonance, Biomolecular; D010766:Phosphorylation; D011487:Protein Conformation; D055503:Protein Multimerization; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000737:chemistry; D000099211:Phospholamban
chemical_list: D002118:Calcium; D002135:Calcium-Binding Proteins; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000099211:Phospholamban