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Molecular Basis of Signaling Mechanisms Mediated by G Proteins

Heidi Hamm
Professor and Chair, Department of Pharmacology
432 MRB-I
615-343-3533 (office)

My work is focused on understanding the molecular basis of signaling mechanisms mediated by G proteins, which are switch proteins. G proteins are normally active, but a receptor that has received a specific signal can activate G proteins, leading to changes in the activity of enzymes that produce second messengers such as cyclic AMP and calcium. The research in my laboratory is aimed at understanding how G proteins become activated by receptors, how they in turn activate effector enzymes, and how they turn off. We determined the sites of interaction between proteins using a method of decomposing the proteins into small synthetic peptides and determining which peptides blocked interaction sites. To understand the process more fully, we determined the atomic structure of the proteins in collaboration with the group of Paul Sigler. We used X-ray crystallography to solve the three-dimensional structures of G proteins in their inactive and activated forms. These high-resolution structural studies allowed us to postulate specific hypotheses regarding mechanisms of receptor: G protein interaction and activation, G protein subunit association- dissociation and effector activation.