Structural Electron Microscopy Team

Team Leader: Dr Ed Morris

Location: Chester Beatty Laboratories, London

Section: Section of Structural Biology

A significant number of proteins relevant to cancer exist as part of large protein complexes: to properly understand their mode of action structural analysis of the intact complexes is required. It is difficult to determine the structures of large complexes by standard crystallographic or NMR techniques because they may only be available in small amounts and limited concentration and are hard to crystallize. Structural electron microscopy is an alternative approach. It involves imaging large numbers of identical particles stabilised at low temperatures in vitreous ice in the electron microscope (cryo-electron microscopy). These images are then processed computationally to derive three-dimensional structural information at much higher resolution than is available in individual molecular images. The structural electron microscopy team focuses on the structural analysis of large protein complexes using cryo-electron microscopy and image analysis.

 

Existing project areas within the team concern the structure of the inositol-1,4,5-trisphosphate receptor (see figure) and the 26S proteasome. IP3R is a gated Ca2+ channel located in the endoplasmic reticulum membrane, which plays a central role in signal transduction. The 26S proteasome degrades proteins targeted for breakdown by ubiquitination and plays a central role in controlling the levels of proteins such as regulators of the cell cycle and apoptosis.