# GPCR Engineering Yields High-Resolution Structural Insights into β2-Adrenergic Receptor Function

@article{Rosenbaum2007GPCREY,
title={GPCR Engineering Yields High-Resolution Structural Insights into $\beta$2-Adrenergic Receptor Function},
author={Daniel M. Rosenbaum and Vadim Cherezov and Michael A. Hanson and S{\o}ren G. F. Rasmussen and Foon Sun Thian and Tong Sun Kobilka and Hee-Jung Choi and Xiao Jie Yao and William I. Weis and Raymond C. Stevens and Brian K. Kobilka},
journal={Science},
year={2007},
volume={318},
pages={1266 - 1273}
}
The β2-adrenergic receptor (β2AR) is a well-studied prototype for heterotrimeric guanine nucleotide–binding protein (G protein)–coupled receptors (GPCRs) that respond to diffusible hormones and neurotransmitters. To overcome the structural flexibility of the β2AR and to facilitate its crystallization, we engineered a β2AR fusion protein in which T4 lysozyme (T4L) replaces most of the third intracellular loop of the GPCR (“β2AR-T4L”) and showed that this protein retains near-native pharmacologic… Expand
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#### Paper Mentions

High-Resolution Crystal Structure of an Engineered Human β2-Adrenergic G Protein–Coupled Receptor
Although the location of carazolol in the β2-adrenergic receptor is very similar to that of retinal in rhodopsin, structural differences in the ligand-binding site and other regions highlight the challenges in using rhodopin as a template model for this large receptor family. Expand
Structural Insights into the Dynamic Process of β2-Adrenergic Receptor Signaling.
A loose allosteric coupling of the agonist-binding site and G-protein-coupling interface that may generally be responsible for the complex signaling behavior observed for many GPCRs is demonstrated. Expand
Structural Insights into the Dynamic Process of β2-Adrenergic Receptor Signaling
A loose allosteric coupling of the agonist-binding site and G-protein-coupling interface that may generally be responsible for the complex signaling behavior observed for many GPCRs is demonstrated. Expand
Structure of a β1-adrenergic G-protein-coupled receptor
G-protein-coupled receptors have a major role in transmembrane signalling in most eukaryotes and many are important drug targets. Here we report the 2.7 Å resolution crystal structure of aExpand
β2-Adrenergic Receptor Conformational Response to Fusion Protein in the Third Intracellular Loop.
• Chemistry, Medicine
• Structure
• 2016
Solution NMR data confirm that response of G-protein and arrestin signaling to ligand efficacy is not coupled, and presents evidence for long-range effects between fusion protein and orthosteric binding cavity, which are suppressed by voluminous bound ligands. Expand
• Medicine, Biology
• Methods in enzymology
• 2013
This chapter summarizes the strategies and methods that have been successfully applied to the structural studies of βARs and discusses the spectacular insights into adrenergic receptor function that were obtained from the structures. Expand
Structural equilibrium underlying ligand-dependent activation of β2-adrenoreceptor
• Chemistry, Medicine
• Nature Chemical Biology
• 2020
NMR structural analysis of an active state of the β2-adrenergic receptor defines a unique orientation for the intracellular half of TM6, responsible for G-protein binding, including an equilibrium among three conformations of a key microswitch. Expand
Structure and Function of an Irreversible Agonist-β2 Adrenoceptor complex
A covalent agonist-bound β2AR–T4L fusion protein is designed that can be covalently tethered to a specific site on the receptor through a disulphide bond, and is capable of activating a heterotrimeric G protein. Expand
The Dynamic Process of β2-Adrenergic Receptor Activation
NMR spectroscopy is used to characterize the conformational dynamics of the transmembrane core of the β(2)-adrenergic receptor (β(2)AR), a prototypical GPCR, and shows that for β( 2)AR, unlike rhodopsin, an agonist alone does not stabilize a fully active conformation. Expand
Crystal Structure of the β2Adrenergic Receptor-Gs protein complex
This crystal structure represents the first high-resolution view of transmembrane signalling by a GPCR and the most surprising observation is a major displacement of the α-helical domain of Gαs relative to the Ras-like GTPase domain. Expand

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