# Crystal structure of the human β2 adrenergic G-protein-coupled receptor

@article{Rasmussen2007CrystalSO,
title={Crystal structure of the human $\beta$2 adrenergic G-protein-coupled receptor},
author={S{\o}ren G F Rasmussen and Hee-Jung Choi and Daniel M. Rosenbaum and Tong Sun Kobilka and Foon Sun Thian and Patricia C. Edwards and Manfred Burghammer and Venkata R. P. Ratnala and Ruslan Sanishvili and Robert F. Fischetti and Gebhard F. X. Schertler and William I. Weis and Brian K. Kobilka},
journal={Nature},
year={2007},
volume={450},
pages={383-387}
}
• Published 15 November 2007
• Chemistry, Biology
• Nature
Structural analysis of G-protein-coupled receptors (GPCRs) for hormones and neurotransmitters has been hindered by their low natural abundance, inherent structural flexibility, and instability in detergent solutions. [] Key Result These differences may be responsible for the relatively high basal activity and structural instability of the β2AR, and contribute to the challenges in obtaining diffraction-quality crystals of non-rhodopsin GPCRs.
1,575 Citations
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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 a
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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.
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Analysis of adrenergic receptor ligand-binding mutants within the context of the reported high-resolution structure of β2AR-T4L provides insights into inverse-agonist binding and the structural changes required to accommodate catecholamine agonists.
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Proceedings of the National Academy of Sciences
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Eight new structures of β1AR–M23 are compared, determined from crystallographically independent molecules in four different crystals with three different antagonists bound in the inactive R state and show clear electron density for cytoplasmic loop 3 linking transmembrane helices 5 and 6 that had not been seen previously.
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Angewandte Chemie
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G-protein-coupled receptors (GPCR) are transmembrane proteins responsible for the transmission of extracellular signals into cells. With more than 800 members, they are the largest family of signal

## References

SHOWING 1-10 OF 48 REFERENCES

• Biology, Chemistry
Nature chemical biology
• 2006
It is found that most partial agonists were as effective as full agonists in disrupting the ionic lock, and disruption of this important molecular switch is necessary, but not sufficient, for full activation of the β2-AR.
• Biology
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
• 1989
Genetic analysis of the β‐adrenergic receptor revealed that the ligand binding domain of this receptor involves residues within the hydrophobic core of the protein, and structural similarities among G protein‐linked receptors suggest that this information should help define functionally important regions of other receptors of this class.
• Biology, Chemistry
Proceedings of the National Academy of Sciences of the United States of America
• 2001
The authors' studies, when compared with studies of activation in rhodopsin, indicate a general mechanism for GPCR activation; however, a notable difference is the relatively slow kinetics of the conformational changes in the β2AR, which may reflect the different energetics of activation by diffusible ligands.
• Biology
The Journal of Biological Chemistry
• 2001
Evidence for the existence of an ionic lock that constrains the relative mobility of the cytoplasmic ends of TM3 and TM6 in the inactive state of the β2-adrenergic receptor is provided and ionic interactions between Asp/Glu3.49, Arg3.50, and Glu6.30 may constitute a common switch governing the activation of many rhodopsin-like G-protein-coupled receptors.
• Biology, Chemistry
Proceedings of the National Academy of Sciences
• 2007
To determine the role of group-conserved residues in the β2-adrenergic receptor (β2-AR), amino acid replacements guided by molecular modeling were carried out at key positions in transmembrane helices H2–H4 and allow insights into the roles of these residues in GPCR structure and function.
• Biology, Chemistry
Chembiochem : a European journal of chemical biology
• 2002
Heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors (GPCRs) respond to a variety of different external stimuli and activate G proteins. GPCRs share many structural
• Biology, Chemistry
The Journal of Biological Chemistry
• 1997
It is proposed that the mutation that confers constitutive activity to the β2 adrenergic receptor removes some stabilizing conformational constraints, allowing CAM to more readily undergo transitions between the inactive and the active states and making the receptor more susceptible to denaturation.
• Biology, Chemistry
Journal of Biological Chemistry
• 2005
Catechol is used as a molecular probe to identify mechanistic differences between β2AR activation by catecholamine agonists, such as isoproterenol, and by the structurally related non-catechol partial agonist salbutamol, showing unexpected differences in binding and activation by structurally similar agonists and partial agonists.
• Biology
Biochemistry
• 2001
The further refinement of rhodopsin is described and some clues about how the receptor could be activated by light are provided, to allow models, firmly based on the atomic-resolution structural information, to be further tested as to the conformational changes that these receptors undergo in going from the quiescent to the signaling state.