The therapeutic potential of orphan adhesion G-protein-coupled receptors - PubMed
5 hours ago
- #therapeutic targets
- #structural biology
- #G-protein-coupled receptors
- Adhesion G-protein-coupled receptors (aGPCRs) play a crucial role in various human pathologies such as cancer, psychiatric disorders, and autoimmune diseases.
- aGPCRs feature a large N terminus with the GPCR autoproteolysis-inducing domain, enabling complex activation mechanisms through cis and trans signalling.
- Recent advancements in structural biology, especially cryogenic electron microscopy, have enhanced understanding of aGPCR activation and facilitated the development of small-molecule agonists and antibody-based therapeutic strategies.
- The review discusses the roles of aGPCRs in human diseases and animal models, insights into their structure-function relationships, and potential therapeutic applications.
- The GAIN domain is highlighted as a key structural module driving autoproteolysis in aGPCRs, crucial for their activation and function.