Matthias Buck, PhD

Protein-Protein Interactions in Cell Signaling of small GTPases, Plexin and Eph receptors

We characterize protein-protein interactions and seek to determine how they form the molecular basis of mechanisms in cell signaling. For these studies, we use a range of structural biology, computational as well as biophysics tools, and we also collaborate with cell biologists. Both the structure and dynamics of signaling proteins are important for signal transduction. We want to understand their molecular determinants and thus their role; for example, what protein structural and dynamic features give rise to binding affinity and to the specificity that selects one protein binding partner over others? These studies will allow give us insight into the normal functions of the signaling proteins and how they are disrupted in diseased states. The knowledge gained will also help us in screening for small molecule agents that can be used to manipulate protein-protein interactions (and consequently signaling in cells) in a chemical biology approach. Furthermore, we develop methods that assist in the identification of interactions in protein complexes and improve their structural representation and characterization by molecular dynamics calculations. Of late our focus has expanded to include the transmembrane helices of receptors. We are interested in understanding how signals are transmitted across the cellular membrane via the receptor’s transmembrane helices and what role the protein domain - bilayer interactions play in the process.