Methods for measuring the thermodynamic stability of membrane proteins.

Learning how amino acid sequences define protein structure has been a major challenge for molecular biology since the first protein structures were determined in the 1960s. In contrast to the staggering progress with soluble proteins, investigations of membrane protein folding have long been hampered by the lack of high-resolution structures and the technical challenges associated with studying the folding process in vitro. In the past decade, however, there has been an explosion of new membrane protein structures and a slower but notable increase in efforts to study the factors that define these structures. Here we review the methods that have been used to evaluate the thermodynamic stability of membrane proteins and provide some salient examples of how the methods have been used to begin to understand the energetics of membrane protein folding.