Epitopes described in "Crystal structure of the β2 adrenergic receptor-Gs protein complex."

Article Authors:Søren G F Rasmussen; Brian T DeVree; Yaozhong Zou; Andrew C Kruse; Ka Young Chung; Tong Sun Kobilka; Foon Sun Thian; Pil Seok Chae; Els Pardon; Diane Calinski; Jesper M Mathiesen; Syed T A Shah; Joseph A Lyons; Martin Caffrey; Samuel H Gellman; Jan Steyaert; Georgios Skiniotis; William I Weis; Roger K Sunahara; Brian K Kobilka
Article Title:Crystal structure of the β2 adrenergic receptor-Gs protein complex.
Reference Detail
Reference ID:1024911
Abstract:G protein-coupled receptors (GPCRs) are responsible for the majority of cellular responses to hormones and neurotransmitters as well as the senses of sight, olfaction and taste. The paradigm of GPCR signalling is the activation of a heterotrimeric GTP binding protein (G protein) by an agonist-occupied receptor. The (2) adrenergic receptor ((2)AR) activation of Gs, the stimulatory G protein for adenylyl cyclase, has long been a model system for GPCR signalling. Here we present the crystal structure of the active state ternary complex composed of agonist-occupied monomeric (2)AR and nucleotide-free Gs heterotrimer. The principal interactions between the (2)AR and Gs involve the amino- and carboxy-terminal -helices of Gs, with conformational changes propagating to the nucleotide-binding pocket. The largest conformational changes in the (2)AR include a 14 Å outward movement at the cytoplasmic end of transmembrane segment 6 (TM6) and an -helical extension of the cytoplasmic end of TM5. The most surprising observation is a major displacement of the -helical domain of Gs relative to the Ras-like GTPase domain. This crystal structure represents the first high-resolution view of transmembrane signalling by a GPCR.
Affiliations:Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, California 94305, USA.
Reference Type:Literature
PubMed ID:21772288
Journal Volume:477
Article Pages:549-55
Journal ISSN:1476-4687
Article Chemical List:Adrenergic beta-2 Receptor Agonists;Multiprotein Complexes;Receptors, Adrenergic, beta-2;GTP-Binding Protein alpha Subunits, Gs
Article MeSH List:Adrenergic beta-2 Receptor Agonists(chemistry; metabolism); Animals; Catalytic Domain; Cattle; Crystallization; Crystallography, X-Ray; Enzyme Activation; GTP-Binding Protein alpha Subunits, Gs(chemistry; metabolism); Models, Molecular; Multiprotein Complexes(chemistry; metabolism); Protein Binding; Rats; Receptors, Adrenergic, beta-2(chemistry; metabolism)
Curation Last Updated:2015-06-07 20:16:40