The DOI matches its Crossref record; 48 of the 48 references it cites were found in a registry or an index.
Crystal structure of the β2 adrenergic receptor–Gs protein complex
Open accessAbstract
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“For example, ligand binding to beta-adrenergic receptors (ARs) results in a conformational change that activates Gs protein complexes [78].”
From G protein-coupled receptors function as cell membrane receptors for the steroid hormone 20-hydroxyecdysone (2020) · cites this paper as [78]
In the citing paper
“In classical GPCR signaling pathways, ligands bind to cell surface transmembrane receptors, such as the β2 ARs, and cause conformational changes in their transmembrane and intracellular domains [48].”
From G-protein-coupled receptor participates in 20-hydroxyecdysone signaling on the plasma membrane (2014) · cites this paper as [48]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
[20] Processing of X-ray diffraction data collected in oscillation mode
Otwinowski, Z., & Minor, W. (1997) · Methods in Enzymology · doi:10.1016/s0076-6879(97)76066-x · Cited by 33,475
Coot : model-building tools for molecular graphics
Emsley, P., & Cowtan, K. (2004) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444904019158 · Cited by 30,571
Phaser crystallographic software
McCoy, A. J., Grosse-Kunstleve, R. W., Adams, P. D., Winn, M. D., Storoni, L. C., & Read, R. J. (2007) · Journal of Applied Crystallography · doi:10.1107/s0021889807021206 · Cited by 20,612
MolProbity : all-atom structure validation for macromolecular crystallography
Chen, V. B., Arendall, W. B., Headd, J. J., Keedy, D. A., Immormino, R. M., Kapral, G. J., Murray, L. W., Richardson, J. S., & Richardson, D. C. (2010) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444909042073 · Cited by 14,115
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
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-citationTransduction of Receptor Signals by ß-Arrestins
Lefkowitz, R. J., & Shenoy, S. K. (2005) · Science · doi:10.1126/science.1109237 · Cited by 1,729
Structure of a nanobody-stabilized active state of the β2 adrenoceptor
Rasmussen, S. G. F., Choi, H., Fung, J. J., Pardon, E., Casarosa, P., Chae, P. S., DeVree, B. T., Rosenbaum, D. M., Thian, F. S., Kobilka, T. S., et al. (2011) · Nature · doi:10.1038/nature09648 · Cited by 1,709
Self-citationSolving structures of protein complexes by molecular replacement with Phaser
McCoy, A. (2006) · Acta Crystallographica Section D: Biological Crystallography · doi:10.1107/s0907444906045975 · Cited by 1,672
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-citationCloning 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
Self-citationHeterotrimeric G protein activation by G-protein-coupled receptors
Oldham, W. M., & Hamm, H. E. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2299 · Cited by 1,234
The structure of the G protein heterotrimer Giα1β1γ2
Wall, M. A., Coleman, D. E., Lee, E. N., Iñiguez-Lluhı́, J. A., Posner, B. A., Gilman, A. G., & Sprang, S. R. (1995) · Cell · doi:10.1016/0092-8674(95)90220-1 · Cited by 1,140
G PROTEIN MECHANISMS: Insights from Structural Analysis
Sprang, S. R. (1997) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.66.1.639 · Cited by 1,057
Structure and function of an irreversible agonist-β2 adrenoceptor complex
Rosenbaum, D. M., Zhang, C., Lyons, J. A., Holl, R., Aragão, D., Arlow, D. H., Rasmussen, S. G. F., Choi, H., DeVree, B. T., Sunahara, R. K., et al. (2011) · Nature · doi:10.1038/nature09665 · Cited by 771
Self-citationRefinement of severely incomplete structures with maximum likelihood inBUSTER–TNT
Blanc, E., Roversi, P., Vonrhein, C., Flensburg, C., Lea, S. M., & Bricogne, G. (2004) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444904016427 · Cited by 719
Strong, M., Sawaya, M. R., Wang, S., Phillips, M. L., Cascio, D., & Eisenberg, D. S. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0602606103 · Cited by 704
Whorton, M. R., Bokoch, M. P., Rasmussen, S. G. F., Huang, B., Zare, R. N., Kobilka, B. K., & Sunahara, R. K. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0611448104 · Cited by 686
Self-citationCrystal structure of metarhodopsin II
Choe, H.-W., Kim, Y. J., Park, J. H., Morizumi, T., Pai, E. F., Krauß, N., Hofmann, K. P., Scheerer, P., & Ernst, O. P. (2011) · Nature · doi:10.1038/nature09789 · Cited by 663
Crystallizing membrane proteins using lipidic mesophases
Caffrey, M., & Cherezov, V. (2009) · Nature Protocols · doi:10.1038/nprot.2009.31 · Cited by 662
Self-citationDimerization: An Emerging Concept for G Protein–Coupled Receptor Ontogeny and Function
Angers, S., Salahpour, A., & Bouvier, M. (2002) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.42.091701.082314 · Cited by 587
Azzi, M., Charest, P. G., Angers, S., Rousseau, G., Kohout, T. A., Bouvier, M., & Piñeyro, G. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1936664100 · Cited by 522
Relationship between the beta-adrenergic receptor and adenylate cyclase.
Ross, E. M., Maguire, M. E., Sturgill, T. W., Biltonen, R. L., & Gilman, A. G. (1977) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)40089-5 · Cited by 485
The structural basis of agonist-induced activation in constitutively active rhodopsin
Standfuss, J., Edwards, P. C., D’Antona, A. M., Fransen, M. P., Xie, G., Oprian, D. D., & Schertler, G. F. X. (2011) · Nature · doi:10.1038/nature09795 · Cited by 481
Chae, P. S., Rasmussen, S. G. F., Rana, R. R., Gotfryd, K., Chandra, R., Goren, M. A., Kruse, A. C., Nurva, S., Loland, C. J., Pierre, Y., et al. (2010) · Nature Methods · doi:10.1038/nmeth.1526 · Cited by 460
Self-citationStructural elements of Gα subunits that interact with Gβγ, receptors, and effectors
Conklin, B. R., & Bourne, H. R. (1993) · Cell · doi:10.1016/0092-8674(93)90245-l · Cited by 419
A G protein-coupled receptor at work: the rhodopsin model
Hofmann, K. P., Scheerer, P., Hildebrand, P. W., Choe, H.-W., Park, J. H., Heck, M., & Ernst, O. P. (2009) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2009.07.005 · Cited by 376
Crystal Structure of the Adenylyl Cyclase Activator G s α
Sunahara, R. K., Tesmer, J. J. G., Gilman, A. G., & Sprang, S. R. (1997) · Science · doi:10.1126/science.278.5345.1943 · Cited by 311
Self-citationSeven transmembrane receptors: something old, something new
Lefkowitz, R. J. (2007) · Acta Physiologica · doi:10.1111/j.1365-201x.2007.01693.x · Cited by 308
Banères, J., & Parello, J. (2003) · Journal of Molecular Biology · doi:10.1016/s0022-2836(03)00439-x · Cited by 275
Super-resolution biomolecular crystallography with low-resolution data
Schroeder, G. F., Levitt, M., & Brünger, A. T. (2010) · Nature · doi:10.1038/nature08892 · Cited by 269
Cerione, R. A., Codina, J., Benovic, J., Lefkowitz, R. J., Birnbaumer, L., & Caron, M. G. (1984) · Biochemistry · doi:10.1021/bi00315a003 · Cited by 249
Structural flexibility of the Gαs α-helical domain in the β 2 -adrenoceptor Gs complex
Westfield, G., Rasmussen, S. G. F., Su, M., Dutta, S., DeVree, B. T., Chung, K. Y., Calinski, D. M., Vélez-Ruiz, G. A., Oleskie, A. N., Pardon, E., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1113645108 · Cited by 230
Self-citationHydrophobic amino acid in the i2 loop plays a key role in receptor-G protein coupling.
Moro, O., Lameh, J., Högger, P., & Sadée, W. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)41524-4 · Cited by 218
Reconstitution of catecholamine-stimulated guanosine triphosphatase activity
Brandt, D. R., Asano, T., Pedersen, S. E., & Ross, E. M. (1983) · Biochemistry · doi:10.1021/bi00288a002 · Cited by 213
G Protein–Coupled Receptor Oligomerization
Breitwieser, G. E. (2004) · Circulation Research · doi:10.1161/01.res.0000110420.68526.19 · Cited by 201
Separate GTP Binding and GTPase Activating Domains of a Gα Subunit
Markby, D. W., Onrust, R., & Bourne, H. R. (1993) · Science · doi:10.1126/science.8266082 · Cited by 179
Kobilka, B. K. (1995) · Analytical Biochemistry · doi:10.1006/abio.1995.1533 · Cited by 166
Self-citationEps, N. V., Preininger, A. M., Alexander, N. S., Kaya, A. İ., Meier, S., Meiler, J., Hamm, H. E., & Hubbell, W. L. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1105810108 · Cited by 162
A robust bulk-solvent correction and anisotropic scaling procedure
Afonine, P. V., Grosse‐Kunstleve, R. W., & Adams, P. D. (2005) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444905007894 · Cited by 157
Receptor-Mediated Activation of Heterotrimeric G-Proteins: Current Structural Insights
Johnston, C. A., & Siderovski, D. P. (2007) · Molecular Pharmacology · doi:10.1124/mol.107.034348 · Cited by 144
Domanska, K., Vanderhaegen, S., Srinivasan, V., Pardon, E., Dupeux, F., Márquez, J. A., Giorgetti, S., Stoppini, M., Wyns, L., Bellotti, V., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1008560108 · Cited by 116
Self-citationAllosteric Modulation of β2-Adrenergic Receptor by Zn2+
Swaminath, G., Steenhuis, J. J., Kobilka, B. K., & Lee, T. W. (2002) · Molecular Pharmacology · doi:10.1124/mol.61.1.65 · Cited by 99
Self-citationThe β-Adrenergic Receptor Is a Substrate for the Insulin Receptor Tyrosine Kinase
Baltensperger, K., Karoor, V., Paul, H., Ruoho, A. E., Czech, M., & Malbon, C. C. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.2.1061 · Cited by 99
Membrane Protein Crystallization in Lipidic Mesophases with Tailored Bilayers
Misquitta, L. V., Misquitta, Y., Cherezov, V., Slattery, O., Mohan, J. M., Hart, D. J., Zhalnina, M. V., Cramer, W. A., & Caffrey, M. (2004) · Structure · doi:10.1016/j.str.2004.09.020 · Cited by 89
Self-citationComplexes between photoactivated rhodopsin and transducin: progress and questions
Jastrzębska, B., Tsybovsky, Y., & Palczewski, K. (2010) · Biochemical Journal · doi:10.1042/bj20100270 · Cited by 46
Research works printed but not linked: 1
- Chung, K. Y. et al. β2 adrenergic receptor-induced conformational changes in the heterotrimeric G protein Gs. Nature 10.1038/nature10488 (this issue) · DOI
Cited by
Sorted by citations
Roth, B. L. (2016) · Neuron · doi:10.1016/j.neuron.2016.01.040 · Cited by 1,742
Molecular signatures of G-protein-coupled receptors
Venkatakrishnan, A., Deupí, X., Lebon, G., Tate, C. G., Schertler, G. F. X., & Babu, M. M. (2013) · Nature · doi:10.1038/nature11896 · Cited by 1,534
Crystal structure of the µ-opioid receptor bound to a morphinan antagonist
Manglik, A., Kruse, A. C., Kobilka, T. S., Thian, F. S., Mathiesen, J. M., Sunahara, R. K., Pardo, L., Weis, W. I., Kobilka, B. K., & Granier, S. (2012) · Nature · doi:10.1038/nature10954 · Cited by 1,400
Self-citationThe Molecular Basis of G Protein–Coupled Receptor Activation
Weis, W. I., & Kobilka, B. K. (2018) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-060614-033910 · Cited by 1,227
Self-citationMicrobial and Animal Rhodopsins: Structures, Functions, and Molecular Mechanisms
Ernst, O. P., Lodowski, D. T., Elstner, M., Hegemann, P., Brown, L. S., & Kandori, H. (2013) · Chemical Reviews · doi:10.1021/cr4003769 · Cited by 1,171
Metadata
- Authors
- Rasmussen, S. G. F., DeVree, B. T., Zou, Y., Kruse, A. C., Chung, K. Y., Kobilka, T. S., Thian, F. S., Chae, P. S., 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., & Kobilka, B. K.
- Affiliations
- University of Copenhagen (DK)
- University of Michigan (US)
- Stanford Medicine (US)
- University of Wisconsin–Madison (US)
- Vrije Universiteit Brussel (BE)
- Trinity College Dublin (IE)
- Corresponding author
- Sunahara, Roger K.
- Kobilka, Brian K.
- ORCID
- Venue
- Nature
- Published
- 2011-07-19
- Volume
- 477
- Issue
- 7366
- Pages
- 549-555
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC3184188
- OpenAlex
- W2167857702
- Cited by
- 3,009
- References
- 48
- Citations by year
- 2026: 93 · 2025: 145 · 2024: 159 · 2023: 147 · 2022: 161 · 2021: 168 · 2020: 177 · 2019: 195 · 2018: 212 · 2017: 234 · 2016: 238 · 2015: 258 · 2014: 255 · 2013: 301 · 2012: 202
- FWCI
- 107.61
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Scopus (Elsevier) (submittedVersion)
- VUBIR (Vrije Universiteit Brussel) (submittedVersion)
- Funders
- Sundhed og Sygdom, Det Frie Forskningsråd
- Science Foundation Ireland (07/IN.1/B1836)
- Fonds Wetenschappelijk Onderzoek
- Lundbeckfonden (R19-2008-2113, R37-2009-3457)
- Danmarks Frie Forskningsfond
- Vlaamse regering
- H. Lundbeck A/S
- National Institutes of Health (GM56169, GM75915)
- National Institute of General Medical Sciences (R01GM075915, U54GM094599, GM083118, GM 56169, P01GM075913, P01 GM75913, R01GM083118, P50GM073210, T32GM008270, GM75915, R01GM056169, R01GM068603)
- National Institute of Diabetes and Digestive and Kidney Diseases (P60DK020572, P60 DK 20572)
- National Institute of Neurological Disorders and Stroke (NS-028471, R01NS028471, R37NS028471)
- 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
- beta2-adrenergic receptor, Gs protein, G protein-coupled receptors, G protein-coupled receptor signaling, adenylate cyclase, GPCR crystal structures, protein dynamics
- MeSH terms
- Animals, Cattle, Crystallization, Enzyme Activation, Models, Molecular, Protein Binding, Receptors, Adrenergic, beta-2, Crystallography, X-Ray, GTP-Binding Protein alpha Subunits, Gs, Catalytic Domain, Multiprotein Complexes, Rats, Adrenergic beta-2 Receptor Agonists
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
