The dos and don'ts of handling membrane proteins for structural studies

Up to 30% of all open reading frames in cells are predicted to encode membrane proteins, and their importance in many biological pathways as well as their role in diseases is unquestionable. Intensive structure-function studies on all classes of membrane proteins have been launched. This combined effort in membrane protein biophysics and biochemistry led to tremendous progress in understanding the function of membrane proteins based on structural, biochemical, functional, bioinformatics and spectroscopic data. Despite all these efforts, the investigation of membrane proteins remains a challenge. In particular, determination of the structure of a membrane protein is still costly in terms of time and resources and has an uncertain payoff. Here, we will summarize techniques and important facts about the structural biology of membrane proteins to reveal functionally meaningful structural information.