Pentameric Phospholamban Structure and Controversy

Abstract

This paper discusses a controversy regarding the structure of the phospholamban pentamer, focusing on two recent papers (1,2). Phospholamban (PLB) is a 52-amino-acid protein that regulates the sarcoplasmic reticulum calcium ATPase (SERCA). It is primarily helical and exists in equilibrium between monomeric and pentameric forms. In 2005, two atomic structural models were published in the above-mentioned papers. In both models, the transmembrane portion of the PLB pentamer is tightly packed and approximately perpendicular to the bilayer, but the two models differ dramatically in the orientation of the cytoplasmic domain. Robia et al. used in-gel fluorescence anisotropy to measure distances between equivalent amino acids at several different positions in the cytoplasmic domain in the subunits of the phospholamban (PLB) pentamer in sodium dodecylsulfate (SDS) micelles (1). The corresponding intrapentameric distances increased as the labeling site approached the N terminus, supporting a “pinwheel” structure for PLB, in which the cytoplasmic domains are splayed apart, approximately parallel to the membrane plane (1). In contrast, Oxenoid et al., performed NMR on PLB in dodecydecylphosphocholine (DPC) micelles, and concluded that the cytoplasmic domains are approximately perpendicular to the membrane plane (2). This paper discusses possible explanations for this discrepancy, including the different sample conditions and different spectroscopic techniques used in the two studies.