In this paper, we analyzed the ground and excited states of phospholamban (PLN), a membrane protein that regulates sarcoplasmic reticulum calcium ATPase (SERCA), in different membrane mimetic environments. Previously, we proposed that the conformational equilibria of PLN are central to SERCA regulation. Here, we show that these equilibria detected in micelles and bicelles are also present in native sarcoplasmic reticulum lipid membranes as probed by MAS solid-state NMR. Importantly, we found that the kinetics of conformational exchange and the extent of ground and excited states in detergent micelles and lipid bilayers are different, revealing a possible role of the membrane composition on the allosteric regulation of SERCA. Since the extent of excited states is directly correlated to SERCA inhibition, these findings open up the exciting possibility that calcium transport in the heart can be controlled by the lipid bilayer composition. This article is part of a Special Issue entitled: Membrane protein structure and function.
Bibliographical noteFunding Information:
We thank Dan Mullen for synthesis of AFA-PLN protein, Rahel Woldeyes for testing AFA-PLN activity. This work was supported by the National Institute of Health ( GM64742 to G.V.) and a pre-doctoral fellowship to M.G. from the American Heart Association ( 10PRE3860050 ).
- Excited states
- Lipid bilayers
- Magic angle spinning
- Membrane protein