Membrane proteins are of central importance for health and disease. They are major targets of today’s pharmaceutical research, and account for over 25% of the proteins predicted by DNA analysis. In spite of this, only ~300 membrane protein structures are known, compared to over 37,000 soluble protein structures. This is because all aspects of handling membrane proteins – isolation, purification, crystallization - are difficult. Electron microscopy removes the need to crystallize these proteins in three-dimensions allowing them to be examined in a detergent-solubilised form or in the 'close-to-native' environment of a lipid bi-layer.
Our aim: To determine the atomic structure of specifically selected membrane proteins and understand how they function in the cell.
Our focus: To obtain optimal electron microscopy (EM) grids for the membrane proteins, to optimize imaging protocols, to develop novel analysis software.
We primarily employ three EM approaches. These deliver complementary information at different resolutions. Single particle cryo electron microscopy (cryo-EM) visualises purified membrane protein complexes surrounded by a detergent micelle, and can achieve atomic resolution. Electron crystallography and electron tomography visualise the complexes while they are embedded in a lipid bilayer or the native membrane. Our FEI Titan Krios or Polara transmission electron microscopes used for this.