Our lab studies the molecular basis of G protein-coupled receptor (GPCR)-mediated signal transduction, principally via the technique of X-ray crystallography. GPCRs are responsible for the sensations of sight and smell, for regulation of blood pressure and heart rate, and for many other cellular events. By determining atomic structures of these signaling proteins both alone and in complex with their various targets, we provide important insights into the molecular basis of signal transduction and of diseases that emerge as a result of dysfunctional signaling.
- X-ray crystallography
- Cardiovascular therapeutics
John Tesmer is a structural biologist who investigates a particular class of protein molecules that carry signals transduced across the membranes of cells, called G proteins. This mechanism of cell-to-cell communication is required for the sensations of sight and smell, for regulation of blood pressure and heart rate, and for many other physiological events.
A medication usually used to help treat depression and anxiety disorders has the potential to help prevent heart failure, according to research published recently by the laboratory of John Tesmer.
Tesmer’s team found that paroxetine, a selective serotonin reuptake inhibitor (SSRI) sold under the name Paxil, inhibits G protein-coupled receptor kinase 2 (GRK2), a protein kinase that becomes over-expressed when people have heart failure. Although so-called “off target” effects are known for many commonly used drugs, this is the first report that identified a direct link between a specific SSRI and a protein target in this signal system.
Nance MR, Kreutz B, Tesmer VM, Sterne-Marr R, Kozasa T, Tesmer JJG (2013). Structural and functional analysis of the regulator of G protein signaling 2 (RGS2)-Gαq complex. Structure, in press.
Lyon AM, Dutta S, Boguth CA, Skiniotis G, Tesmer JJG (2013). Structure of full-length phospholipase C β3 in complex with Gαq reveals functional interfaces of its C-terminal coiled-coil domain. Nature Struct. Mol. Biol., in press.