What can we learn from a small regulatory membrane protein?

This chapter reviews the molecular biology, biochemical, and NMR methods that we used to study the structural dynamics, membrane topology, and interaction of phospholamban (PLN), a small regulatory membrane protein involved in the regulation of the sarcoplasmic reticulum Ca-ATPase (SERCA). In particular, we show the progression of our research from the initial hypotheses toward understanding the molecular mechanisms of SERCA's regulation, including the effects of PLN oligomerization and posttranslational phosphorylation. Finally, we show how the knowledge of the molecular mechanism of the structural dynamics and topology of free and bound proteins can lead to the rational design of PLN analogs for possible use in gene therapy.