National Center for
2M3B: Serine 16 phosphorylated phospholamban pentamer, Hybrid solution and solid-state NMR structural ensemble
Structural dynamics and topology of phosphorylated phospholamban homopentamer reveal its role in the regulation of calcium transport
Structure (2013) 21 p.2119-2130
Phospholamban (PLN) inhibits the sarco(endo)plasmic reticulum Ca(2)(+)-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 A long and 2 A in diameter, which is inconsistent with canonical Ca(2)(+)-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.