Chris Tate

Integral membrane proteins are fundamental to a cell's survival, allowing the import of nutrients, the export of toxins and intercellular communication via receptors. We aim to understand the processes of solute translocation and receptor signalling processes by determining the structures of important and interesting membrane proteins by X-ray crystallography. Particular focuses of the lab are G protein-coupled receptors (GPCRs), neurotransmitter transporters and bacterial multidrug transporters.

There are over 350 non-odorant GPCRs encoded by the human genome that are involved in hormone binding and transducing this signal to the cytoplasm, resulting in the activation of G protein pathways and eventually eliciting a cellular response. The key role of GPCRs in signal transduction pathways makes them ideal as drug targets with many classes of small molecule drugs, such as beta blockers or anti-asthma treatments, either inhibiting or activating these receptors. There are many potential problems in determining the structure of membrane proteins, but we have recently developed a strategy based on rational mutagenesis to improve the thermostability of GPCRs, which has made crystallisation and structure determination far more tractable. We initially solved the structure of the β₁-adrenergic receptor to 2.7 Å resolution with an antagonist bound and recently structures have been solved with agonists bound. Subsequent work will focus on determining the structures of different conformational states of the β₁, adenosine A_2A and neurotensin receptors, bound to G proteins and arresting.