Receptor-Arrestin Interactions: The GPCR Perspective

Biomolecules

Mehdi Gharghabi¹  EugeniaV. Gurevich²  VsevolodV. Gurevich²  Mohammad Seyedabadi³ 

[1] Department of Cancer Biology and Genetics, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA;Department of Pharmacology, Vanderbilt University, Nashville, TN 37232, USA;Department of Toxicology & Pharmacology, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari 48471-93698, Iran;

关键词: arrestin;    GPCR;    protein–protein interactions;    signaling;    conformational change;   

DOI  :  10.3390/biom11020218

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown