High-Field Solid-State NMR of the Transmembrane Domain of the Epidermal Growth Factor Receptor ErbB-2

Supervisors: Steven Brown and Ann Dixon

Despite comprising over 30% of the proteins encoded in the human genome, and playing crucial roles in many cellular processes, transmembrane proteins are currently among the least well characterised substances in biology. This lack of information is a direct consequence of the natural environment of these proteins; they are embedded within the lipid bilayers that surround cells, and as such, extracting structural information using established crystal diffraction and solution-state NMR methods is challenging. Solid-state NMR techniques have the potential to be a site specific probe of these systems, for which experiments can be performed upon samples within hydrated lipid environments to reveal key structural features.

The Epidermal growth factor receptor ErbB-2 is a membrane protein of key biological interest. It is responsible for triggering cell division, however it is vulnerable to a mutation in its transmembrane (TM) domain, resulting in oncogenic activity. 3-D structures of the extracellular and intracellular regions of this protein have been obtained, however the molecular structure of the TM domain is still a matter of dispute. Since the TM domain is known to be the site of key protein-protein interactions, a structural study of this region is of great importance in understanding the biological function of ErbB-2 and its role in disease. Solid-state NMR is one of very few methods that can provide structural information for this protein in a native-like bilayer environment.

Contact:

Natalie Ellis
Magnetic Resonance Centre
Millburn House
University of Warwick
Coventry
CV4 7AL

Tel: 024 761 50812
Internal: 50812
Email: n dot s dot ellis at warwick dot ac dot uk