Solid-state NMR and synchrotron circular dichroism of a receptor tyrosine kinase transmembrane segment and its interactions with a viral oncoprotein

Membrane proteins and polypeptides are key players in many biological processes, as they control the flow of information and material between cells and their environment, and they are prime drug targets. The focus of our group lies on the structure-function analysis transmembrane protein segments of cell surface receptors. We are especially interested to find out how they insert into the membrane, how they fold and align within the hydrophobic core of the bilayer, how they find and bind to their corresponding interaction partners to fulfil their biological
functions, and what is going wrong in disease. Synchrotron circular dichroism, oriented circular dichroism and 2D solid-state PISEMA NMR measurements on macroscopically aligned samples are used to determine the conformation, alignment and dynamics of these proteins in the quasinative environment of a lipid bilayer. Here, we will present two interacting proteins: the PDGF-receptor β (PDGFR), a receptor tyrosine kinase, that gets activated by the small oncogenic E5 protein from papillomavirus through highly specific transmembrane helix-helix interactions [1,2]. A complementary PISEMA-NMR and CD analysis of the PDGFR transmembrane domain and the E5 protein was used to resolve the structures and orientations of both proteins in the lipid bilayer [3,4,5,6].