2m3b

Publication Abstract from PubMed

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 A long and 2 A 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.

Structural Dynamics and Topology of Phosphorylated Phospholamban Homopentamer Reveal Its Role in the Regulation of Calcium Transport.,Vostrikov VV, Mote KR, Verardi R, Veglia G Structure. 2013 Oct 22. pii: S0969-2126(13)00358-4. doi:, 10.1016/j.str.2013.09.008. PMID:24207128^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.