G protein-coupled receptors. II. Mechanism of agonist activation

• Published in: The Journal of biological chemistry 1998-07, Vol.273 (29), p.17979-17982
• Main Authors: Gether, U, Kobilka, B K
• Format: Article
• Language: English
• Subjects: Animals; GTP-Binding Proteins; Humans; Models, Molecular; Protein Conformation; Receptors, Cell Surface - agonists
• ISSN: 0021-9258
• DOI: 10.1074/jbc.273.29.17979

The majority of transmembrane signal transduction in response to hormones and neurotransmitters is mediated by G protein-coupled receptors (GPCRs). Moreover, GPCRs are the principal signal transducers for the senses of sight and smell. GPCRs are characterized by seven membrane-spanning domains with an extracellular N terminus and a cytoplasmic C terminus. Based on certain key sequences, GPCRs can be divided into three major subfamilies, receptors related to rhodopsin (type A), receptors related to the calcitonin receptor (type B), and receptors related to the metabotropic receptors (type C). Of these, the rhodopsin subfamily is by far the largest and most extensively investigated and will be the focus of the present review. This review will examine current progress in addressing a fundamental question in the field of GPCR-mediated signal transduction: the nature of the physical changes in receptors that link agonist binding to G protein activation. It will explore the differences and similarities in the activation of rhodopsin and other GPCRs by focusing on two questions. What conformational changes take place during receptor activation? How do agonists induce these conformational changes in the receptor?