Speaker:             

Dr Doryen Bubeck                         

Title:                     

Cryo electron microscopy reveals how the membrane attack complex punctures lipid bilayers. 

Abstract: 

Cryo-electron microscopy (cryoEM) is a technique used to visualize large macromolecular complexes in a frozen hydrated state. Recent advances in data acquisition and image processing have enabled scientists to visualize complex biological assemblies in atomic detail. Here we use cryoEM to understand how the complement system destroys Gram negative bacteria. Complement is a fundamental component of the human immune system; central to the battle between hosts and pathogens. The membrane attack complex (MAC) is the direct killing arm of complement that acts by forming large pores in target cell membranes. Uncontrolled activation results in by-stander damage, which can have devastating consequences for host cells and impact inflammatory pathologies, thrombosis and cancer. Results from my lab have revealed the molecular mechanism underpinning MAC assembly. We have defined the stoichiometry of the complex and identified interaction interfaces that determine its sequential assembly mechanism. Recent data from my lab has now revealed atomic resolution information for the complete transmembrane pore. These results have provided a molecular and biophysical basis for MAC pore formation, which has led to a general mechanism for how proteins cross lipid bilayers.       

Host:                    

Dr Rivka Isaacson   

Location:                    

Room 106, Britannia House

If you are not part of the Department of Chemistry, but are interested in attending, please contact: manuel.muller@kcl.ac.uk