The role of lipids in defining membrane protein interactions: insights from mass spectrometry

Cellular membranes comprise hundreds of lipids in which protein complexes, such as ion channels, receptors, and scaffolding complexes, are embedded. These protein assemblies act as signalling and trafficking platforms for processes fundamental to life. Much effort in recent years has focused on identifying the protein components of these complexes after their extraction from the lipid membrane in detergent micelles. Spectacular advances have been made using X-ray crystallography, providing in some cases detailed information about the mechanism of pumping and channel gating. These structural studies are leading to a growing realisation that, to understand their function, it is not only the structures of the protein components that are important but also knowledge of the protein–lipid interactions. This review highlights recent insights gained from this knowledge, surveys methods being developed for probing these interactions, and focuses specifically on the potential of mass spectrometry in this growing area of research.