Abstract

Integral membrane proteins play a wide variety of roles in normal cell function and disease. As such they are also important drug targets, accounting for more than 50% of the targets of all currently prescribed therapeutics. Whilst substantial progress has been made in the structural and functional characterisation of membrane proteins there are still hurdles, most particularly with respect to eukaryotic membrane proteins. My laboratory have spent many years optimising our approaches to production of membrane proteins for structural studies. We have adopted and indeed in some cases pioneered methods including protein engineering, characterisation and application of novel detergents and exploring and exploiting the role of membrane lipids in stabilising membrane proteins. Here I will cover how we have successfully transferred stabilising mutations between integral membrane transporter families, how novel detergents allowed us to access a very problematic membrane transporter for structural analysis and describe the development of a new screen allowing identification of lipids that stabilise an individual membrane protein.