Our lab seeks to understand the molecular mechanisms of integral membrane proteins involved in eukaryotic and mammalian cell signaling and regulation. We are using protein engineering, X-ray crystallography, and spectroscopy to study the structure and dynamics of molecules involved in hormone signaling and lipid homeostasis.
As depicted in the movie above, recent X-ray structures have uncovered the conformational transition between inactive and active conformations of the beta2 adrenergic receptor that is promoted by binding of agonists such as adrenaline. Due to major advances in the structural and biophysical characterization of G protein-coupled receptors, we now know as much about how this protein works as any other physiologically-significant mammalian receptor.
Harnessing these advances for other classes of membrane proteins will reveal important insights into fundamental processes such as the homeostatic regulation of cellular cholesterol by the SREBP pathway. In addition, these efforts may enable the design of new classes of small molecules that modulate key signaling pathways by controlling protein conformational changes within cellular membranes.