Cited by 2,534Receptor Mechanisms and SignalingProtein Kinase Regulation and GTPase SignalingNeuroscience and Neuropharmacology Research

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The structure and function of G-protein-coupled receptors

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Rosenbaum, Daniel M., Rasmussen, Søren G. F., Kobilka, Brian K.·2009·Nature

DOI 10.1038/nature08144PMC PMC3967846

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Abstract

G-protein-coupled receptors (GPCRs) mediate most of our physiological responses to hormones, neurotransmitters and environmental stimulants, and so have great potential as therapeutic targets for a broad spectrum of diseases. They are also fascinating molecules from the perspective of membrane-protein structure and biology. Great progress has been made over the past three decades in understanding diverse GPCRs, from pharmacology to functional characterization in vivo. Recent high-resolution structural studies have provided insights into the molecular mechanisms of GPCR activation and constitutive activity.

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Crystal Structure of Rhodopsin: A G Protein-Coupled Receptor
Palczewski, K., Kumasaka, T., Hori, T., Behnke, C. A., Motoshima, H., Fox, B. A., Trong, I. L., Teller, D. C., Okada, T., Stenkamp, R. E., et al. (2000) · Science · doi:10.1126/science.289.5480.739 · Cited by 5,637
High-Resolution Crystal Structure of an Engineered Human β 2 -Adrenergic G Protein–Coupled Receptor
Cherezov, V., Rosenbaum, D. M., Hanson, M. A., Rasmussen, S. G. F., Thian, F. S., Kobilka, T. S., Choi, H., Kühn, P., Weis, W. I., Kobilka, B. K., et al. (2007) · Science · doi:10.1126/science.1150577 · Cited by 3,280
Self-citation
[19] Integrated methods for the construction of three-dimensional models and computational probing of structure-function relations in G protein-coupled receptors
Ballesteros, J. A., & Weinstein, H. (1995) · Methods in neurosciences · doi:10.1016/s1043-9471(05)80049-7 · Cited by 3,001 · cited 1×
“48 (human β 2 AR, with Ballesteros/Weinstein numberin”
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Fredriksson, R., Lagerström, M. C., Lundin, L.-G., & Schiöth, H. B. (2003) · Molecular Pharmacology · doi:10.1124/mol.63.6.1256 · Cited by 2,941 · cited 1×
“GPCRs in vertebrates are commonly divided into five families on the basis of their sequence and structural similarity”
Crystal structure of the human β2 adrenergic G-protein-coupled receptor
Rasmussen, S. G. F., Choi, H., Rosenbaum, D. M., Kobilka, T. S., Thian, F. S., Edwards, P. C., Burghammer, M. C., Ratnala, V. R. P., Sanishvili, R., Fischetti, R. F., et al. (2007) · Nature · doi:10.1038/nature06325 · Cited by 1,935
Self-citation
The 2.6 Angstrom Crystal Structure of a Human A 2A Adenosine Receptor Bound to an Antagonist
Jaakola, V., Griffith, M. T., Hanson, M. A., Cherezov, V., Chien, E. Y. T., Lane, J. R., IJzerman, A. P., & Stevens, R. C. (2008) · Science · doi:10.1126/science.1164772 · Cited by 1,786
A ternary complex model explains the agonist-specific binding properties of the adenylate cyclase-coupled beta-adrenergic receptor.
Léan, A. D., Stadel, J. M., & Lefkowitz, R. J. (1980) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(20)79672-9 · Cited by 1,606
Structure of a β1-adrenergic G-protein-coupled receptor
Warne, T., Serrano‐Vega, M. J., Baker, J. G., Moukhametzianov, R., Edwards, P. C., Henderson, R. A., Leslie, A. G. W., Tate, C. G., & Schertler, G. F. X. (2008) · Nature · doi:10.1038/nature07101 · Cited by 1,377
GPCR Engineering Yields High-Resolution Structural Insights into β 2 -Adrenergic Receptor Function
Rosenbaum, D. M., Cherezov, V., Hanson, M. A., Rasmussen, S. G. F., Thian, F. S., Kobilka, T. S., Choi, H., Yao, X.-J., Weis, W. I., Stevens, R. C., et al. (2007) · Science · doi:10.1126/science.1150609 · Cited by 1,335
Self-citation
Cloning of the gene and cDNA for mammalian β-adrenergic receptor and homology with rhodopsin
Dixon, R. A. F., Kobilka, B. K., Strader, D. J., Benovic, J., Dohlman, H. G., Frielle, T., Bolanowski, M. A., Bennett, C. D., Rands, E., Diehl, R. E., et al. (1986) · Nature · doi:10.1038/321075a0 · Cited by 1,275 · cited 1×
“The clustering of these residues in the cytoplasmic half of the transmembrane bundle reflects the basic conservation of mechanism across GPCRs, a remarkable structural affirmation of a hypothesis made more than 20 years ag”
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Background
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Background
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Background
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Background
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Wright, D. B., Tripathi, S., Sikarwar, A. S., Santosh, K., Perez‐Zoghbi, J. F., Ojo, O. O., Irechukwu, N., Ward, J. P. T., & Schaafsma, D. (2012) · Pulmonary Pharmacology & Therapeutics · doi:10.1016/j.pupt.2012.06.005 · Cited by 44
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Yagi, H., Asanoma, K., Ohgami, T., Ichinoe, A., Sonoda, K., & Kato, K. (2016) · Oncogene · doi:10.1038/onc.2015.505 · Cited by 42
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Lee, Y., Kim, S., Choi, S., & Hyeon, C. (2016) · Biophysical Journal · doi:10.1016/j.bpj.2016.08.002 · Cited by 41
New approaches towards the understanding of integral membrane proteins: A structural perspective on G protein‐coupled receptors
Grisshammer, R. (2017) · Protein Science · doi:10.1002/pro.3200 · Cited by 43
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Shirafkan, N., Shomali, N., Kazemi, T., Shanehbandi, D., Ghasabi, M., Baghbani, E., Ganji, M., Khaze, V., Mansoori, B., & Baradaran, B. (2018) · Journal of Cellular Biochemistry · doi:10.1002/jcb.28164 · Cited by 42
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Love, A. C., & Wagner, G. P. (2021) · Evolution · doi:10.1111/evo.14421 · Cited by 43
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Marco, I., Valhondo, M., Martín‐Fontecha, M., Vázquez‐Villa, H., Rı́o, J. D., Planas, A. M., Sagredo, O., Ramos, J. A., Torrecillas, I. R., Pardo, L., et al. (2011) · Journal of Medicinal Chemistry · doi:10.1021/jm2007886 · Cited by 42
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“…of the helix conformation around a proline kink) in TM6 causing key sequences to be exposed to cytoplasmic binding partners and a conformational change of Y residue of the NPXXY motif located in TM7 stabilizing the active conformation (Rosenbaum et al., 2009, 2011; Rasmussen et al., 2011).”
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“Transduction of ligandinduced responses by GPCRs follows a series of standard structural alterations from outside to inside the cell [34, 37, 38].”
BackgroundInfluential
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Background
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“Monoamine receptors, primarily G protein-coupled receptors (GPCRs), except for the 5-HT3 receptor (a ligand-gated ion channel) (14), are involved in cellular responses to neurotransmitters and the modulation of in ﬂ ammation.”
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Zhang, J., Feng, H., Xu, S., & Feng, P. (2016) · Biochemical Pharmacology · doi:10.1016/j.bcp.2016.03.021 · Cited by 39
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Authors: Rosenbaum, D. M., Rasmussen, S. G. F., & Kobilka, B. K.
Affiliations: Stanford Medicine (US)
ORCID: Rasmussen, Søren G. F.
Kobilka, Brian K.
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2009-05
Volume: 459
Issue: 7245
Pages: 356-363
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/nature08144
PMC: PMC3967846
OpenAlex: W1988097700
Cited by: 2,534
References: 73
Citations by year: 2026: 108 · 2025: 171 · 2024: 175 · 2023: 140 · 2022: 196 · 2021: 177 · 2020: 150 · 2019: 172 · 2018: 122 · 2017: 136 · 2016: 132 · 2015: 120 · 2014: 133 · 2013: 135 · 2012: 146
FWCI: 11.79
Type: journal article
Language: en
Open access: green
europepmc.org
Licence: www.springer.com/tdm (tdm)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
RePEc: Research Papers in Economics (submittedVersion)
Funders: Lundbeckfonden (R19-2008-2113)
National Institute of General Medical Sciences (F32GM082028, R01GM083118)
National Institute of Neurological Disorders and Stroke (R01NS28471, R01NS028471)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords: G protein-coupled receptors, GPCR structure, GPCR activation, constitutive activity, membrane protein structure, therapeutic target, hormone signaling, neurotransmitter signaling
MeSH terms: Animals, Cytoplasm, Humans, Protein Conformation, Signal Transduction, Conserved Sequence, Receptors, G-Protein-Coupled, Opsins

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The structure and function of G-protein-coupled receptors

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