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Title: Crystal structure of the [beta subscript 2] adrenergic receptor–Gs protein complex

Crystal structure of the [beta subscript 2] adrenergic receptor–Gs protein complex 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 {beta}{sub 2} adrenergic receptor ({beta}{sub 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 {beta}{sub 2}AR and nucleotide-free Gs heterotrimer. The principal interactions between the {beta}{sub 2}AR and Gs involve the amino- and carboxy-terminal {alpha}-helices of Gs, with conformational changes propagating to the nucleotide-binding pocket. The largest conformational changes in the {beta}{sub 2}AR include a 14 {angstrom} outward movement at the cytoplasmic end of transmembrane segment 6 (TM6) and an {alpha}-helical extension of the cytoplasmic end of TM5. The most surprising observation is a major displacement of the {alpha}-helical domain of G{alpha}s relative to the Ras-like GTPase domain. This crystal structure represents the first high-resolution view of transmembrane signalling by a GPCR.
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Publication Date:
OSTI Identifier:OSTI ID: 1026537
Resource Type:Journal Article
Resource Relation:Journal Name: Nature; Journal Volume: 477; Journal Issue: 09, 2011
Research Org:Advanced Photon Source (APS), Argonne National Laboratory (ANL), Argonne, IL (US)
Sponsoring Org:FOREIGNNIH
Country of Publication:United States
Language:ENGLISH
Subject: 59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES; BIOLOGY; BIOPHYSICS; CONFORMATIONAL CHANGES; CRYSTAL STRUCTURE; HORMONES; PROTEINS; RECEPTORS; SYMPATHOMIMETICS