Crystal structure of the β2 adrenergic receptor-Gs protein complex.

TitleCrystal structure of the β2 adrenergic receptor-Gs protein complex.
Publication TypeJournal Article
Year of Publication2011
AuthorsRasmussen, S. G. F., Devree B. T., Zou Y., Kruse A. C., Chung K. Young, Kobilka T. Sun, Thian F. Sun, Chae P. Seok, Pardon E., Calinski D., Mathiesen J. M., Shah S. T. A., Lyons J. A., Caffrey M., Gellman S. H., Steyaert J., Skiniotis G., Weis W. I., Sunahara R. K., and Kobilka B. K.
JournalNature
Volume477
Issue7366
Pagination549-55
Date Published2011 Sep 29
ISSN1476-4687
KeywordsAdrenergic beta-2 Receptor Agonists, Animals, Catalytic Domain, Cattle, Crystallization, Crystallography, X-Ray, Enzyme Activation, GTP-Binding Protein alpha Subunits, Gs, Models, Molecular, Multiprotein Complexes, Protein Binding, Rats, Receptors, Adrenergic, beta-2
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 β(2) adrenergic receptor (β(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 β(2)AR and nucleotide-free Gs heterotrimer. The principal interactions between the β(2)AR and Gs involve the amino- and carboxy-terminal α-helices of Gs, with conformational changes propagating to the nucleotide-binding pocket. The largest conformational changes in the β(2)AR include a 14 Å outward movement at the cytoplasmic end of transmembrane segment 6 (TM6) and an α-helical extension of the cytoplasmic end of TM5. The most surprising observation is a major displacement of the α-helical domain of Gαs relative to the Ras-like GTPase domain. This crystal structure represents the first high-resolution view of transmembrane signalling by a GPCR.

DOI10.1038/nature10361
Alternate JournalNature
PubMed ID21772288
PubMed Central IDPMC3184188
Grant ListGM083118 / GM / NIGMS NIH HHS / United States
GM56169 / GM / NIGMS NIH HHS / United States
GM75915 / GM / NIGMS NIH HHS / United States
NS028471 / NS / NINDS NIH HHS / United States
P01 GM75913 / GM / NIGMS NIH HHS / United States
P50GM073210 / GM / NIGMS NIH HHS / United States
P60DK-20572 / DK / NIDDK NIH HHS / United States
R01 GM068603 / GM / NIGMS NIH HHS / United States
R01 GM068603-01 / GM / NIGMS NIH HHS / United States
R01 GM068603-02 / GM / NIGMS NIH HHS / United States
R01 GM068603-03 / GM / NIGMS NIH HHS / United States
R01 GM068603-04 / GM / NIGMS NIH HHS / United States
R01 GM068603-05 / GM / NIGMS NIH HHS / United States
T32-GM008270 / GM / NIGMS NIH HHS / United States
U54GM094599 / GM / NIGMS NIH HHS / United States
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