Abstract

The realisation that the lipid environment is crucial for maintaining the structure and function of membrane proteins prompts new methods to understand lipid interactions. One such method, mass spectrometry, is emerging with the potential to monitor different modes of lipid binding to membrane protein complexes. Initial studies monitored the addition of lipids and deduced the kinetic and thermodynamic effects of lipid binding to proteins. Recently however, we have focused on identifying lipids already present, explicitly in plugs, annular rings or cavities. Lipids that bind within these orifices to membrane proteins will have higher residence times than those in the bulk lipid bilayer and consequently can be quantified and characterized by mass spectrometry. In special cases, lipids identified within cavities have been proposed as substrates following activity assays. Alternatively, a gas phase unfolding protocol can be used to distinguish lipids that are important for stability. In this lecture I will provide an overview of recent advances in mass spectrometry, with a particular focus on the distinction of the various modes of lipid binding, their implications for structure and function, as well as new directions that lie ahead.