John Tesmer

Our Research

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.

About John Tesmer

Specialties:
  • X-ray crystallography
  • Pharmacology
  • 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.

Research Highlight: Paxil for heart failure?

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.

Recent Publications

Azevedo AW, Doan T, Moaven H, Sokal I, Baameur F, Vishnivetskiy SA, Homan KT, Tesmer JJG, Gurevich VV, Chen J, Rieke F: C-terminal threonines and serines play distinct roles in the desensitization of rhodopsin, a G protein-coupled receptor. Elife 2015;4. doi: 10.7554/eLife.05981. PMCID: in process.PubMed Link

Li L, Homan KT, Vishnivetskiy SA, Manglik A, Tesmer JJG, Gurevich VV, Gurevich EV. G protein-coupled receptor kinases of the GRK4 subfamily phosphorylate inactive GPCRs. J. Biol. Chem. 2015, 290: 10775-90. PMCID: 4409243 PubMedLink

Glukhova A, Hinkovska-Galcheva V, Kelly R, Abe A, Shayman JA, Tesmer JJG: Structure and function of lysosomal phospholipase A2 and lecithin: cholesterol acyltransferase. Nat. Commun.2015, 6:6250. doi: 10.1038/ncomms7250. PMCID: 4397983 PubMed Link