Scientists built 7,500 versions of a single cell-surface receptor to map how drugs trigger cellular responses, generating over 150,000 measurements for the target protein.
Researchers at the Centro de Regulación Genómica developed the method to study G protein-coupled receptors, a family of 800 molecular structures that sit on cell surfaces and transmit external signals like hormones, neurotransmitters, and metabolites, Salud a Diario reported. Approximately one in every three approved medications worldwide targets this protein family, including antihistamines, beta-blockers, opioids, and asthma inhalers.
Because the architecture across these 800 receptors is similar, drugs often bind to unintended targets and cause accidental side effects.
Targeting Respiratory Receptors
The study focused on the beta-2 adrenergic receptor, a G protein-coupled receptor that directs cells to relax airway passages and serves as the target for chronic obstructive pulmonary disease and asthma medications like salbutamol and salmeterol, as detailed in Nature Structural & Molecular Biology.
Researchers synthesized thousands of protein variants by swapping individual building blocks. Each of the 7,500 versions was introduced into human cells and tested across varying drug dosages and parameters.
The resulting data revealed hidden pharmacological targets. Many regions feature adjustable positions that fine-tune receptor behavior, which could allow for precise control over cellular responses.
“You can have a diagram perfect of the parts that work of a protein and still you do not know what happens when you change a component,” said Taylor Mighell, a researcher at the Catalan institution, told Salud a Diario. “Now, we have something more similar to a manual than to a diagram.”
Unlocking Precision Medicine
To test whether the technique functions beyond a single receptor, the team applied it to a second protein involved in kidney water regulation and observed comparable results. The long-term objective is to construct similar maps for additional members of the receptor family.
The project changes how drugs are discovered, building on a history that began with screening thousands of compounds without fully understanding their mechanisms, followed by structure-based design in the 1990s that earned a Nobel Prize in 2012.
“Because of their unique function in the reception and transmission of signals are excellent pharmacological targets,” Mighell told SINC.
Common Questions About G Protein-Coupled Receptors and Medications
How many G protein-coupled receptors exist in the human body?
There are 800 different types of these receptors, which allow cells to detect external signals including hormones, neurotransmitters, and light photons, according to research published in Nature Structural & Molecular Biology.
What specific medications target the beta-2 adrenergic receptor?
Inhalable medicines such as salbutamol and salmeterol act upon this specific receptor to treat chronic obstructive pulmonary disease and asthma, as reported by Salud a Diario.
How many total measurements did the researchers generate for the study?
The research team produced more than 150,000 distinct measurements by testing 7,500 synthetic versions of the receptor against different drug dosages and parameters, according to SINC.
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