Mechanism of Activation of the heterotrimeric G protein alpha subunit

G protein-coupled receptors (GPCRs) interact with intracellular heterotrimeric complexes to transduce extracellular signals into cellular responses. These heterotrimeric complexes are composed of an alpha, beta, and gamma subunits. Upon binding an activated receptor, the alpha subunit must undergo a initial conformational change, open to release GDP, bind GTP and undergo an additional “closing” conformation in order to dissociate from beta/gamma and act on downstream effectors. My research project goal is to identify and better understand the network of allosteric interactions required to propagate these conformational changes across the subunit and to the other proteins within the ternary complex. Coupling energy analysis, EPR/DEER-based structural information, and evolutionarily insight, my project works to refine our working model of G protein activation.