Format

Send to

Choose Destination
Biochemistry. 2013 Sep 24;52(38):6684-94. doi: 10.1021/bi400517b. Epub 2013 Sep 11.

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

Author information

1
Division of Molecular Biosciences, Imperial College London , London SW7 2AZ, U.K.

Abstract

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.

PMID:
23968132
PMCID:
PMC3844793
DOI:
10.1021/bi400517b
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for American Chemical Society Icon for PubMed Central
Loading ...
Support Center