The thousands of such receptors throughout the body play a fundamental role in the mechanisms of sight, smell and taste, and in regulating heart rate, blood pressure and glucose metabolism. The receptors are by far the most common target for drugs that affect cardiac output, blood pressure and many other physiological functions. Thus, said the researchers, their fundamental discovery could guide pharmaceutical companies in creating a new class of drugs that aim not at blocking the receptors themselves, but at modulating the machinery that regulates them. Such drugs could treat a range of disorders from congestive heart failure to Parkinson's disease, they said.
The newly revealed structure of this receptor "off-switch" -- called a G protein-coupled receptor kinase (GRK) -- reveals the protein as the molecular equivalent of a three-armed octopus, with independent segments capable of performing multiple regulatory functions at once. Kinases are enzymes that act as molecular switches by adding phosphates to other proteins.
The researchers -- led by Howard Hughes Medical Institute investigator Robert Lefkowitz at Duke University Medical Center and John Tesmer of the University of Texas at Austin -- reported their findings in the May 23, 2003, issue of the journal Science. The team also included scientists from the University of Texas at Austin and University College London. Also on the research team was Darrell Capel of Duke.