Scientists report that they have characterized a previously unknown link in the chain of biochemical reactions implicated in some forms of heart disease.
Researchers have known for some time that patients suffering from high blood pressure release hormones such as angiotensin that can trigger an abnormal growth of cardiac cells that sometimes leads to heart disease. These hormones, after binding to receptors on the surface of cells, activate G-alpha-q. Further along in the signaling pathway, RhoA, a protein that regulates cell growth and gene expression, has also been tied to heart disease.
In the current study, the investigators obtained X-ray crystallographic images of G-alpha-q, RhoA, and one of the intermediaries that relay cellular signals from G-alpha-q to RhoA. The team then determined the atomic structure of the intermediary, an enzyme called p63RhoGEF.
“We’ve trapped all three proteins together and we’ve learned how they interact,” points out team leader, John Tesmer, Ph.D., a research associate professor at the Life Sciences Institute and an associate professor at the Medical School at the University of Michigan. “Essentially, it’s a previously unrecognized pathway that one could target to treat cardiovascular disease.”
Concurrently, animal studies conducted by colleagues at the University of Heidelberg confirmed the interactions between these substances as well as their importance to smooth muscle function.
Investigators from the University of Texas, Austin were also involved in the study. The work is reported in the December 21 edition of Science.