Cardiovascular diseases remain a leading cause of death around the world. A primary contributor to these afflictions is high blood pressure, or hypertension.
While treatments exist for the condition, which affects tens of millions of Americans, these remedies are not without side effects, and some variants of the disorder are treatment-resistant. The need for more effective therapies to address hypertension-related disease is therefore acute.The illustration shows a portion of the receptor pGC-A, known as the extracellular domain, which protrudes from cell surfaces in the cardiovascular system. Small molecules bind with the receptor and exert subtle control over blood pressure. The new research offers the first sneak peek at the full-length receptor, a vital step in the development of new drugs to treat hypertension and other afflictions.
To accomplish this however, biologists need more detailed maps of the mechanisms underlying cardiovascular regulation. One such regulator is a protein receptor that sits atop cardiovascular cells, acting as a conduit for messages that are transmitted when specific hormone molecules bind with them.
Known as pGC-A, this membrane receptor acts a bit like a thermostat, sensitively adjusting the body’s blood pressure to maintain a homeostatic balance essential for health. The receptor acts not only as a vital cellular component for vascular and cardiac homeostasis, but also plays an important role in lipid metabolism and is implicated in cancer development.
In a new study, published in the current issue of the journal Scientific Reports, researchers from Arizona State University’s Biodesign Center for Applied Structural Discovery and their colleagues, in collaboration with Mayo Clinic, Rochester, make critical progress toward unveiling the structure of pGC-A.
The study provides the first purification, characterization and preliminary structural analysis of the full-length protein receptor. The research advances include crystallizing the protein and showing that these crystals diffract X-rays — two critical steps essential to solving the structure.
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