Models for the Transmembrane Region of the Phospholamban Pentamer: Which Is Correct?a

Phospholamban is a 52-amino acid protein that assembles into a pentamer in the membranes of the sarcoplasmic reticulum. Pentamer formation is driven in large part by interactions of the transmembrane regions of the protein, which are thought to be arranged as interacting alpha-helices. The structural properties of phospholamban have been studied by mutagenesis and optical spectroscopy, resulting in a large database. In this discussion, we present advances in computational modeling, which identifies two probable structures for the transmembrane pentamer. A new approach to mutagenesis is described, which should lead to a clear distinction between the two possible models.