Receptor-Arrestin Interactions: The GPCR Perspective

Arrestins are a small family of four proteins in most vertebrates that bind hundreds of different G protein-coupled receptors (GPCRs). Arrestin binding to a GPCR has at least three functions: precluding further receptor coupling to G proteins, facilitating receptor internalization, and initiating distinct arrestin-mediated signaling. The molecular mechanism of arrestin-GPCR interactions has been extensively studied and discussed from the arrestin perspective, focusing on the roles of arrestin elements in receptor binding. Here, we discuss this phenomenon from the receptor perspective, focusing on the receptor elements involved in arrestin binding and emphasizing existing gaps in our knowledge that need to be filled. It is vitally important to understand the role of receptor elements in arrestin activation and how the interaction of each of these elements with arrestin contributes to the latter's transition to the high-affinity binding state. A more precise knowledge of the molecular mechanisms of arrestin activation is needed to enable the construction of arrestin mutants with desired functional characteristics.

Automated summary

Arrestins are a small family of proteins found in most vertebrates, binding to a variety of G protein-coupled receptors and playing key roles in preventing further receptor-G protein coupling, promoting receptor internalization, and initiating specific signaling pathways. Research on the molecular mechanisms of arrestin-GPCR interactions has focused on arrestin elements in receptor binding, but further investigations are needed on the receptor elements involved in arrestin binding to fill existing knowledge gaps. Understanding how receptor elements activate arrestin and contribute to high-affinity binding is crucial for developing arrestin mutants with desired functional characteristics.