PUBLICATION HIGHLIGHT
New insights into how antibodies regulate GPCR signaling
This publication highlight is part of the SBGrid/Meharry Medical College Communities Project, focused on science education and demonstrating how structural biology and preclinical science connect to medicine.
G-Protein Coupled Receptors, or GPCRs, are a large family of proteins that are found in the plasma membrane of cells. GPCRs help facilitate a wide variety of cellular functions in response to different stimuli. Binding of hormones and neurotransmitters as well as external signals like light and smells can activate GPCRs and cause a different cellular response depending on what pathway is activated. Because of their diverse range of functions in the body, many medications work by targeting GPCRs. Although many of these drugs are successful at targeting GPCRs and helping to treat diseases, these drugs often lack a certain specificity needed to regulate different subclasses of GPCRs. A lack of specificity in the types of GPCRs that drugs can bind to is what increases the chances of side effects in the person taking the drug. While antibodies could limit the risk of side effects, since they are naturally more selective for certain proteins, their properties as GPCR ligands are still not well understood. In order to bridge this gap, a new study looks at how antibodies can potentially modulate the angiotensin II type I receptor, AT1R. AT1R helps regulate renal and cardiovascular function in response to the hormone angiotensin II. To date, AT1R is one of the most successfully drugged GPCRs. Angiotensin receptor small-molecule blockers are commonly prescribed in the treatment of high blood pressure.
The article titled Antibodies Expand the Scope of Angiotensin Receptor Pharmacology, published by SBGrid member Andew Kruse from Harvard Medical School, explores the use of engineered antibodies, called nanobodies, to enhance targeting of angiotensin receptors. This study shows that nanobodies can selectively bind to angiotensin receptors with high affinity and specificity. These nanobodies not only block the receptor’s function but can also modulate its signaling pathways in unique ways that traditional small molecules cannot achieve. This approach may allow for more precise medications in the future, especially for diseases related to the angiotensin system such as hypertension and heart failure, with fewer side effects compared to conventional therapies. This breakthrough could lead to significant advancements in cardiovascular medicine and the development of more effective therapies for a range of conditions.
Read more in Nature Chemical Biology.
By KeAndreya Morrison, Meharry Medical College
KeAndreya Morrison is a 4th year biomedical sciences Ph.D. Candidate at Meharry Medical College studying the relationship between host and pathogen through the lens of structural biology. KeAndreya is a Georgia native where she completed her bachelor’s degree in biology at Fort Valley State University in Fort Valley, GA.
