Structural highlights
FunctionPPLA_RABIT Phospholamban has been postulated to regulate the activity of the calcium pump of cardiac sarcoplasmic reticulum. Publication Abstract from PubMedPhospholamban 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 determine the conformations and populations of the ground state and the three main excited states of phospholamban by incorporating nuclear magnetic resonance (NMR) residual dipolar couplings (RDCs) 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 populations of its excited states. These results demonstrate that approach that we describe provides a detailed characterisation of the different states of phospholamban that determine the function and regulation of this membrane protein. We anticipate that the availability of conformational ensembles will provide opportunities for the development of therapeutic strategies to control the activity of phospholamban by modulating the relative populations of its conformational substates. Structures of the Excited States of Phospholamban and Shifts in their Populations upon Phosphorylation.,De Simone A, Gustavsson MB, Montalvao RW, Shi L, Veglia G, Vendruscolo M Biochemistry. 2013 Aug 22. PMID:23968132[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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