Membrane Proteins

More detail+-

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.

Methods+-

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.