Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

Structure of the D2 dopamine receptor bound to the atypical antipsychotic drug risperidone

Nature volume 555, pages 269–273 (2018)Cite this article

Subjects

Abstract

Dopamine is a neurotransmitter that has been implicated in processes as diverse as reward, addiction, control of coordinated movement, metabolism and hormonal secretion. Correspondingly, dysregulation of the dopaminergic system has been implicated in diseases such as schizophrenia, Parkinson’s disease, depression, attention deficit hyperactivity disorder, and nausea and vomiting. The actions of dopamine are mediated by a family of five G-protein-coupled receptors1. The D2 dopamine receptor (DRD2) is the primary target for both typical2 and atypical3,4 antipsychotic drugs, and for drugs used to treat Parkinson’s disease. Unfortunately, many drugs that target DRD2 cause serious and potentially life-threatening side effects due to promiscuous activities against related receptors4,5. Accordingly, a molecular understanding of the structure and function of DRD2 could provide a template for the design of safer and more effective medications. Here we report the crystal structure of DRD2 in complex with the widely prescribed atypical antipsychotic drug risperidone. The DRD2–risperidone structure reveals an unexpected mode of antipsychotic drug binding to dopamine receptors, and highlights structural determinants that are essential for the actions of risperidone and related drugs at DRD2.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Structural details of DRD2 and comparison with DRD3 and DRD4.
Figure 2: Comparison of the ligand-binding pocket across the D2-like family receptors.
Figure 3: Different extended binding pockets revealed across D2-like family receptors.
Figure 4: The hydrophobic ‘patch’ of the DRD2 binding pocket.

Similar content being viewed by others

Accession codes

Primary accessions

Protein Data Bank

References

  1. Missale, C., Nash, S. R., Robinson, S. W., Jaber, M. & Caron, M. G. Dopamine receptors: from structure to function. Physiol. Rev. 78, 189–225 (1998)

    Article  CAS  PubMed  Google Scholar 

  2. Creese, I., Burt, D. R. & Snyder, S. H. Dopamine receptor binding predicts clinical and pharmacological potencies of antischizophrenic drugs. Science 192, 481–483 (1976)

    Article  ADS  CAS  PubMed  Google Scholar 

  3. Meltzer, H. Y., Matsubara, S. & Lee, J.-C. Classification of typical and atypical antipsychotic drugs on the basis of dopamine D-1, D-2 and serotonin2 pKi values. J. Pharmacol. Exp. Ther. 251, 238–246 (1989)

    CAS  PubMed  Google Scholar 

  4. Roth, B. L., Sheffler, D. J. & Kroeze, W. K. Magic shotguns versus magic bullets: selectively non-selective drugs for mood disorders and schizophrenia. Nat. Rev. Drug Discov. 3, 353–359 (2004)

    Article  CAS  PubMed  Google Scholar 

  5. Roth, B. L. Drugs and valvular heart disease. N. Engl. J. Med. 356, 6–9 (2007)

    Article  CAS  PubMed  Google Scholar 

  6. Seeman, P. & Lee, T. Antipsychotic drugs: direct correlation between clinical potency and presynaptic action on dopamine neurons. Science 188, 1217–1219 (1975)

    Article  ADS  CAS  PubMed  Google Scholar 

  7. Sibley, D. R. & Monsma, F. J. Jr. Molecular biology of dopamine receptors. Trends Pharmacol. Sci. 13, 61–69 (1992)

    Article  CAS  PubMed  Google Scholar 

  8. Beaulieu, J. M. & Gainetdinov, R. R. The physiology, signaling, and pharmacology of dopamine receptors. Pharmacol. Rev. 63, 182–217 (2011)

    Article  CAS  PubMed  Google Scholar 

  9. Volkow, N. D., Fowler, J. S., Wang, G. J., Swanson, J. M. & Telang, F. Dopamine in drug abuse and addiction: results of imaging studies and treatment implications. Arch. Neurol. 64, 1575–1579 (2007)

    Article  PubMed  Google Scholar 

  10. Bunzow, J. R. et al. Cloning and expression of a rat D2 dopamine receptor cDNA. Nature 336, 783–787 (1988)

    Article  ADS  CAS  PubMed  Google Scholar 

  11. Grandy, D. K. et al. Cloning of the cDNA and gene for a human D2 dopamine receptor. Proc. Natl Acad. Sci. USA 86, 9762–9766 (1989)

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  12. Monsma, F. J., Jr, McVittie, L. D., Gerfen, C. R., Mahan, L. C. & Sibley, D. R. Multiple D2 dopamine receptors produced by alternative RNA splicing. Nature 342, 926–929 (1989)

    Article  ADS  CAS  PubMed  Google Scholar 

  13. Allen, J. A. et al. Discovery of β-arrestin-biased dopamine D2 ligands for probing signal transduction pathways essential for antipsychotic efficacy. Proc. Natl Acad. Sci. USA 108, 18488–18493 (2011)

    Article  ADS  PubMed  PubMed Central  Google Scholar 

  14. Javitch, J. A., Fu, D., Chen, J. & Karlin, A. Mapping the binding-site crevice of the dopamine D2 receptor by the substituted-cysteine accessibility method. Neuron 14, 825–831 (1995)

    Article  CAS  PubMed  Google Scholar 

  15. Ballesteros, J. A., Shi, L. & Javitch, J. A. Structural mimicry in G protein-coupled receptors: implications of the high-resolution structure of rhodopsin for structure-function analysis of rhodopsin-like receptors. Mol. Pharmacol. 60, 1–19 (2001)

    Article  CAS  PubMed  Google Scholar 

  16. Chien, E. Y. et al. Structure of the human dopamine D3 receptor in complex with a D2/D3 selective antagonist. Science 330, 1091–1095 (2010)

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  17. Wang, S. et al. D4 dopamine receptor high-resolution structures enable the discovery of selective agonists. Science 358, 381–386 (2017)

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  18. Manglik, A. et al. Structure-based discovery of opioid analgesics with reduced side effects. Nature 537, 185–190 (2016)

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  19. Wacker, D., Stevens, R. C. & Roth, B. L. How ligands illuminate GPCR molecular pharmacology. Cell 170, 414–427 (2017)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. McCorvy, J. D. et al. Structure-inspired design of β-arrestin-biased ligands for aminergic GPCRs. Nat. Chem. Biol. 14, 126–134 (2018)

    Article  CAS  PubMed  Google Scholar 

  21. Free, R. B. et al. Discovery and characterization of a G protein-biased agonist that inhibits β-arrestin recruitment to the D2 dopamine receptor. Mol. Pharmacol. 86, 96–105 (2014)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Roberts, D. J. & Strange, P. G. Mechanisms of inverse agonist action at D2 dopamine receptors. Br. J. Pharmacol. 145, 34–42 (2005)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Rasmussen, S. G. et al. Crystal structure of the β2 adrenergic receptor-Gs protein complex. Nature 477, 549–555 (2011)

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  24. Shapiro, D. A., Kristiansen, K., Weiner, D. M., Kroeze, W. K. & Roth, B. L. Evidence for a model of agonist-induced activation of 5–HT2A serotonin receptors which involves the disruption of a strong ionic interaction between helices 3 and 6. J. Biol. Chem. 18, 11441–11449 (2002)

    Article  CAS  Google Scholar 

  25. Ballesteros, J. A. et al. Activation of the β2-adrenergic receptor involves disruption of an ionic lock between the cytoplasmic ends of transmembrane segments 3 and 6. J. Biol. Chem. 276, 29171–29177 (2001)

    Article  CAS  PubMed  Google Scholar 

  26. Palczewski, K. et al. Crystal structure of rhodopsin: a G protein-coupled receptor. Science 289, 739–745 (2000)

    Article  ADS  CAS  PubMed  Google Scholar 

  27. Janssen, P. A. et al. Pharmacology of risperidone (R 64 766), a new antipsychotic with serotonin–S2 and dopamine–D2 antagonistic properties. J. Pharmacol. Exp. Ther. 244, 685–693 (1988)

    CAS  PubMed  Google Scholar 

  28. Kapur, S., Zipursky, R., Jones, C., Remington, G. & Houle, S. Relationship between dopamine D2 occupancy, clinical response, and side effects: a double-blind PET study of first-episode schizophrenia. Am. J. Psychiatry 157, 514–520 (2000)

    Article  CAS  PubMed  Google Scholar 

  29. Kapur, S. & Seeman, P. Does fast dissociation from the dopamine D2 receptor explain the action of atypical antipsychotics?: A new hypothesis. Am. J. Psychiatry 158, 360–369 (2001)

    Article  CAS  PubMed  Google Scholar 

  30. Sykes, D. A. et al. Extrapyramidal side effects of antipsychotics are linked to their association kinetics at dopamine D2 receptors. Nat. Commun. 8, 763 (2017)

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  31. Rosenbaum, D. M. et al. GPCR engineering yields high-resolution structural insights into β2-adrenergic receptor function. Science 318, 1266–1273 (2007)

    Article  ADS  CAS  PubMed  Google Scholar 

  32. Caffrey, M. & Cherezov, V. Crystallizing membrane proteins using lipidic mesophases. Nat. Protocols 4, 706–731 (2009)

    Article  CAS  PubMed  Google Scholar 

  33. Minor, W., Cymborowski, M., Otwinowski, Z. & Chruszcz, M. HKL-3000: the integration of data reduction and structure solution—from diffraction images to an initial model in minutes. Acta Crystallogr. D Biol. Crystallogr. 62, 859–866 (2006)

    Article  CAS  PubMed  Google Scholar 

  34. McCoy, A. J. et al. Phaser crystallographic software. J. Appl. Crystallogr. 40, 658–674 (2007)

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Adams, P. D. et al. PHENIX: a comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr. D Biol. Crystallogr. 66, 213–221 (2010)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Emsley, P., Lohkamp, B., Scott, W. G. & Cowtan, K. Features and development of Coot. Acta Crystallogr. D Biol. Crystallogr. 66, 486–501 (2010)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Motulsky, H. J. & Mahan, L. C. The kinetics of competitive radioligand binding predicted by the law of mass action. Mol. Pharmacol. 25, 1–9 (1984)

    CAS  PubMed  Google Scholar 

  38. Pei, J. & Grishin, N. V. PROMALS3D: multiple protein sequence alignment enhanced with evolutionary and three-dimensional structural information. Methods Mol. Biol. 1079, 263–271 (2014)

    Article  PubMed  PubMed Central  Google Scholar 

  39. Webb, B. & Sali, A. Comparative protein structure modeling using MODELLER. Curr. Protoc. Bioinformatics 47, 5 6 1–5 6 32 (2014)

    Article  Google Scholar 

  40. Coleman, R. G., Carchia, M., Sterling, T., Irwin, J. J. & Shoichet, B. K. Ligand pose and orientational sampling in molecular docking. PLoS One 8, e75992 (2013)

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  41. Southan, C. et al. The IUPHAR/BPS Guide to pharmacology in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. Nucleic Acids Res. 44 (D1), D1054–D1068 (2016)

    Article  CAS  PubMed  Google Scholar 

  42. Mysinger, M. M., Carchia, M., Irwin, J. J. & Shoichet, B. K. Directory of useful decoys, enhanced (DUD-E): better ligands and decoys for better benchmarking. J. Med. Chem. 55, 6582–6594 (2012)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Case, D. A . et al. AMBER 2015. (University of California, 2015)

  44. Word, J. M., Lovell, S. C., Richardson, J. S. & Richardson, D. C. Asparagine and glutamine: using hydrogen atom contacts in the choice of side-chain amide orientation. J. Mol. Biol. 285, 1735–1747 (1999)

    Article  CAS  PubMed  Google Scholar 

  45. Gallagher, K. & Sharp, K. Electrostatic contributions to heat capacity changes of DNA-ligand binding. Biophys. J. 75, 769–776 (1998)

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  46. Sharp, K. A. Polyelectrolyte electrostatics: Salt dependence, entropic, and enthalpic contributions to free energy in the nonlinear Poisson–Boltzmann model. Biopolymers 36, 227–243 (1995)

    Article  CAS  Google Scholar 

  47. Mysinger, M. M. & Shoichet, B. K. Rapid context-dependent ligand desolvation in molecular docking. J. Chem. Inf. Model. 50, 1561–1573 (2010)

    Article  CAS  PubMed  Google Scholar 

  48. Sadowski, J., Gasteiger, J. & Klebe, G. Comparison of automatic three-dimensional model builders using 639 X-ray structures. J. Chem. Inf. Comput. Sci. 34, 1000–1008 (1994)

    Article  CAS  Google Scholar 

  49. Hawkins, P. C., Skillman, A. G., Warren, G. L., Ellingson, B. A. & Stahl, M. T. Conformer generation with OMEGA: algorithm and validation using high quality structures from the Protein Databank and Cambridge Structural Database. J. Chem. Inf. Model. 50, 572–584 (2010)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Chambers, C. C., Hawkins, G. D., Cramer, C. J. & Truhlar, D. G. Model for aqueous solvation based on class IV atomic charges and first solvation shell effects. J. Phys. Chem. 100, 16385–16398 (1996)

    Article  CAS  Google Scholar 

  51. Li, J., Zhu, T., Cramer, C. J. & Truhlar, D. G. New class IV charge model for extracting accurate partial charges from wave functions. J. Phys. Chem. A 102, 1820–1831 (1998)

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by NIH Grants RO1MH61887, U19MH82441, the NIMH Psychoactive Drug Screening Program Contract and the Michael Hooker Chair for Protein Therapeutics and Translational Proteomics (to B.L.R.) and by R35GM122481 (to B.K.S.). We thank J. Sondek and S. Endo-Streeter for providing independent structure quality control analysis; M. J. Miley and the UNC macromolecular crystallization core for advice and use of their equipment for crystal harvesting and transport, which is supported by the National Cancer Institute under award number P30CA016086; B. E. Krumm for advice on data processing and help with thermostabilization assays; and the staff of GM/CA@APS, which has been funded with Federal funds from the National Cancer Institute (ACB-12002) and the National Institute of General Medical Sciences (AGM-12006). This research used resources of the Advanced Photon Source, a US Department of Energy (DOE) Office of Science user facility operated for the DOE Office of Science by Argonne National Laboratory under Contract No. DE-AC02-06CH11357.

Author information

Authors and Affiliations

  1. Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, 27599-7365, North Carolina, USA

    Sheng Wang, Tao Che, Daniel Wacker & Bryan L. Roth

  2. Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, 94158-2280, California, USA

    Anat Levit & Brian K. Shoichet

  3. Division of Chemical Biology & Medicinal Chemistry, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, 27599-7360, North Carolina, USA

    Bryan L. Roth

  4. National Institute of Mental Health Psychoactive Drug Screening Program (NIMH PDSP), School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, 27599-7365, North Carolina, USA

    Bryan L. Roth

Authors
  1. Sheng Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tao Che
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Anat Levit
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Brian K. Shoichet
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Daniel Wacker
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Bryan L. Roth
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

S.W. designed experiments, developed the DRD2 construct and purification, expressed, purified and crystallized the receptor, collected diffraction data, solved and refined the structure, analysed the structure, performed radioligand binding and prepared the manuscript. T.C. performed radioligand binding, analysed the data and assisted with preparing the manuscript. A.L. conducted the homology modelling and docking and helped to edit the manuscript. B.K.S. supervised the modelling and docking and helped to prepare the manuscript. D.W. refined and analysed the structure, supervised the structure determination and assisted with preparing the manuscript. B.L.R. supervised the overall project and management and prepared the manuscript.

Corresponding authors

Correspondence to Sheng Wang, Daniel Wacker or Bryan L. Roth.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Additional information

Reviewer Information Nature thanks D. Sibley and the other anonymous reviewer(s) for their contribution to the peer review of this work.

Publisher's note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Extended data figures and tables

Extended Data Figure 1 Thermostability of DRD2 constructs, crystal packing of the DRD2–risperidone complex and representative electron density of the DRD2 structure.

a, Membranes containing DRD2 or DRD2 with thermostability mutations were heated for 30 min with 1 nM [3H]-N-methylspiperone and the amount of bound [3H]-ligand was determined. b, Purified DRD2–T4L protein (with or without thermostability mutations) was heated with 10 μM risperidone and 1 μM BODIPY FL l-cystine dye using a temperature gradient and the amount of dye bound to unfolding protein was determined. Data were analysed by nonlinear regression and apparent Tm values (transition temperature where 50% of the receptor is inactive) were determined from analysis of the sigmoidal melting curves. All data in a and b are mean ± s.e.m. of three independent assays. c–e, Packing of the DRD2–risperidone complex crystallized in the P212121 spacegroup. DRD2 is shown in green and the T4L-fusion protein is shown in red, or in cyan where it interacts with DRD2. EL1 and EL2 of DRD2 are shown in magenta and blue, respectively. f, 2Fo–Fc electron density map (blue mesh) of risperidone (yellow) contoured at 1σ. g, Fo–Fc omit map (green mesh) contoured at 3.0σ of risperidone (yellow). h, 2 Fo–Fc electron density map of DRD2 binding pocket residues (blue mesh) contoured at 1σ.

Source data

Extended Data Figure 2 Conserved hydrophobic residue of EL2 in all available aminergic receptor structures.

In all panels, receptors are shown as cartoons. Ligands and residues are shown as sticks. a, 5HT1B (PDB code: 4IAR). b, 5HT2B (PDB code: 5TVN). c, DRD2. d, DRD3 (PDB code: 3PBL). e, DRD4 (PDB code: 5WIU). f, ACM1 (PDB code: 5CXV). g, ACM2 (PDB code: 3UON). h, ACM3 (PDB code: 4ADJ). i, ACM4 (PDB code: 4DSG). j, HRH1 (PDB code: 3RZE). k, ADRB1 (PDB code: 2VT4). l, ADRB2 (PDB code: 2RH1). m, DRD2. n, Conserved EL2 hydrophobic residues (red box) are located two residues away from a conserved cysteine that forms a disulphide bridge between EL2 and TMIII. Notable exceptions to the presence of a hydrophobic residue are DRD1 and DRD5, which contain a serine, and HRH1 and HRH4, which contain a threonine and proline, respectively.

Extended Data Figure 3 Comparison of D2 receptors viewed from the extracellular side, and structural alignment with β2AR and A2AR reveals an inactive state of DRD2.

a–d, DRD2, green; DRD3, magenta (PDB code: 3PBL); DRD4, blue (PDB code: 5WIU). Risperidone (yellow), eticlopride (cyan) and nemonapride (light pink) are shown as sticks and spheres. Displacements of H6.55 and Y/V7.35 are shown at DRD2 (a), DRD3 (b) and DRD4 (c). d, Views from the extracellular side of DRD2 and DRD3. e, f, Superposition of TMVI at DRD2 (green), inactive β2AR (yellow, PDB code: 2RH1), active β2AR (light pink, PDB code: 3SN6), inactive A2AR (brown, PDB code: 3REY) and active A2AR (blue, PDB code: 5G53) aligned through helices I–IV. g–j, Cytoplasmic view of alignment between DRD2 and active and inactive β2AR (g, h) or A2AR (i, j). Rearrangements of two highly conserved residues (Y7.53 and R3.50) within the core of the receptor are shown as sticks. Ligands are omitted for clarity and hydrogen bonds are shown as grey dotted lines.

Extended Data Figure 4 Conserved Trp of EL1 in all available aminergic receptor structures shows its unique position in DRD2–risperidone.

Receptors are shown as cartoons. Ligands and residues are shown as sticks. a, Conserved Trp residues of EL1 are shown in red boxes. b, 5HT1B (PDB code: 4IAR). c, 5HT2B (PDB code: 5TVN). d, DRD2. e, DRD3 (PDB code: 3PBL). f, DRD4 (PDB code: 5WIU). g, ACM1 (PDB code: 5CXV). h, ACM2 (PDB code: 3UON). i, ACM3 (PDB code: 4ADJ). j, ACM4 (PDB code: 4DSG). k, HRH1 (PDB code: 3RZE). l, ADRB1 (PDB code: 2VT4). m, ADRB2 (PDB code: 2RH1).

Extended Data Figure 5 Risperidone has distinct poses in solution and in complex with DRD2, and comparison of X-ray structure and model of DRD2.

a, Trp100EL1 determines the configuration of the tetrahydropyridopyrimidinone moiety of risperidone. Structure of unbound risperidone shown in green and DRD2-bound risperidone shown in yellow. b, Electron density (2Fo–Fc maps, blue mesh) for W100EL1 in the DRD2–risperidone complex (contoured at 1.0σ). c, 2Fo–Fc electron density map (blue mesh) of Leu942.64, Trp100EL1, Ile184EL2 and risperidone (yellow) contoured at 0.8σ. d, Overall view of DRD2–risperidone X-ray structure and model. e–h, Comparison of X-ray structure and model of DRD2. In d–h, DRD2 X-ray structure and model are shown as cartoons, with the X-ray structure in green and the model in magenta or blue. Risperidone is shown in the X-ray structure as yellow spheres or sticks, and in the model as cyan or light pink.

Extended Data Figure 6 Patch residues of the DRD2 orthosteric pocket impair the dissociation rates of risperidone, aripiprazole, N-methylspiperone and nemonapride.

a–g, Comparison of risperidone dissociation from wild-type DRD2 (a) and W100EL1A (b), W100EL1L (c), W100EL1F (d), L942.64A (e), I184EL2A (f) or L942.64A/I184EL2A (g) mutants. h–n, Comparison of aripiprazole dissociation from wild-type DRD2 (h) and W100EL1A (i), W100EL1L (j), W100EL1F (k), L942.64A (l), I184EL2A (m) or L942.64A/I184EL2A (n) mutants. o, p, Comparison of N-methylspiperone (o) or nemonapride (p) dissociation from wild-type DRD2 and W100EL1A, W100EL1L or W100EL1F mutants (n = 3). q, r, Comparison of N-methylspiperone (q) or nemonapride (r) dissociation from wild-type DRD2 and L942.64A, I184EL2A or L942.64A/I184EL2A mutants. All data are mean ± s.e.m. of four independent assays (n = 4 independent experiments). Error bars in o–r denote s.e.m. from four independent assays.

Source data

Extended Data Table 1 Affinities of antipsychotic drugs for thermostabilized mutant and wild-type DRD2
Full size table
Extended Data Table 2 Data collection and refinement statistics
Full size table
Extended Data Table 3 Affinity of risperidone and nemonapride for ligand-binding-pocket mutants of the D2 dopamine receptor
Full size table
Extended Data Table 4 Compound dissociation and association rates on wild-type and mutant DRD2
Full size table

Supplementary information

PowerPoint slides

Source data

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, S., Che, T., Levit, A. et al. Structure of the D2 dopamine receptor bound to the atypical antipsychotic drug risperidone. Nature 555, 269–273 (2018). https://doi.org/10.1038/nature25758

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nature25758

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing