In a groundbreaking international effort, scientists at St. Jude Children’s Research Hospital harnessed data science, pharmacology, and structural information to conduct an in-depth investigation into the adrenaline receptor at an atomic level. This receptor, a member of the G protein-coupled receptor (GPCR) family, is the target of a significant portion of FDA-approved drugs. The results of this essential work have been published today in Science.
Imagine taking apart a watch to study how each component contributes to its function. In a similar way, the researchers delved into the β2-adrenergic receptor (β2AR) to understand the role of each amino acid in mediating a signaling response, collaborating with experts from Stanford University, the University of Montreal, the MRC Laboratory of Molecular Biology, and Cambridge University.
“Our approach was to understand how every amino acid influences the functioning of the receptor by mutating them one at a time,” explained co-corresponding author M. Madan Babu, PhD, from St. Jude. “Through evolution, every amino acid in the receptor has been carefully crafted to ensure that it binds to the natural ligand, adrenaline, and produces the appropriate physiological response.”
GPCRs are crucial proteins that connect the cell’s external and internal environments by relaying external signals into the cell. When adrenaline binds to the β2AR, it triggers a response inside the cell, setting off a complex chain of events that result in physiological responses.
These findings shed light on the intricate mechanisms by which adrenaline and GPCRs function, providing crucial insights for developing new therapies that can precisely modulate receptor activity. If you would like to know more, the full article is available here. Read More
