Structures of the excited states of phospholamban and shifts in their populations upon phosphorylation

Alfonso De Simone, Martin Gustavsson, Rinaldo W. Montalvao, Lei Shi, Gianluigi Veglia, Michele Vendruscolo

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


Phospholamban is an integral membrane protein that controls the calcium balance in cardiac muscle cells. As the function and regulation of this protein require the active involvement of low populated states in equilibrium with the native state, it is of great interest to acquire structural information about them. In this work, we calculate the conformations and populations of the ground state and the three main excited states of phospholamban by incorporating nuclear magnetic resonance residual dipolar couplings as replica-averaged structural restraints in molecular dynamics simulations. We then provide a description of the manner in which phosphorylation at Ser16 modulates the activity of the protein by increasing the sizes of the populations of its excited states. These results demonstrate that the approach that we describe provides a detailed characterization of the different states of phospholamban that determine the function and regulation of this membrane protein. We anticipate that the knowledge of conformational ensembles enable the design of new dominant negative mutants of phospholamban by modulating the relative populations of its conformational substates.

Original languageEnglish (US)
Pages (from-to)6684-6694
Number of pages11
Issue number38
StatePublished - Sep 24 2013


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