When
Where
Presenter:
Dr. Michael Brown, Professor, Department of Chemistry and Biochemistry, University of Arizona
Abstract:
G-protein–coupled receptors (GPCRs) are membrane proteins that are the targets of the majority of human pharmaceuticals. Despite structural water in X-ray structures, the biophysical significance of these solvent molecules remains unknown. Here we show that rhodopsin activation in lipid membranes is tightly coupled to bulk water movements into the protein. A surprisingly large number of water molecules floods the protein core to stabilize the effector binding conformation. Our results imply a new model of GPCR activation, in which the protein becomes solvent swollen and partially unfolded up
on forming the active state. We demonstrate the novel mechanism whereby water acts as a powerful allosteric modulator of a pharmacologically important membrane protein family.