Article info 2014 2 (1)    002  (01)   pp.  21 ~ 25
Title Current advances in the development of G-protein-coupled receptor structure and their future application in drug design
Authors Kuglae Kim, Yingjin Kang and Hyun-Soo Cho*
Institutions Department of Systems Biology, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Korea. *Correspondence: hscho8@yonsei.ac.kr
Abstract G-protein-coupled receptors (GPCRs) are seven-transmembrane proteins that play important roles in signal transduction from the extracellular compartment to the cytoplasm. GPCR malfunction has been implicated in various diseases such as cancer, allergy, neuronal disease, rheumatism, and obesity. Because of the importance of GPCRs, GPCR-targeting drugs occupy approximately 40% of the total drug market. Recently, three-dimensional structures of many GPCRs have been successfully ascertained on the basis of various developed methods that improve protein stabilization, crystallization, and diffraction. Some GPCR structures have elucidated the underlying activation mechanism by allowing comparison between the receptor’s inactive and active states. β-adrenergic receptor bound with G-protein trimeric complex (Gαβγ) structure has also been determined. To date, XFEL technology is the latest technology used to determine GPCR structures. In this review, we describe GPCR structures, structure-based activation mechanisms and principles, and the application of XFEL in determining GPCR structures and development of GPCR-based drugs.