Skip to main content

Thank you for visiting 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.

Structural basis of ligand binding modes at the neuropeptide Y Y1 receptor


Neuropeptide Y (NPY) receptors belong to the G-protein-coupled receptor superfamily and have important roles in food intake, anxiety and cancer biology1,2. The NPY–Y receptor system has emerged as one of the most complex networks with three peptide ligands (NPY, peptide YY and pancreatic polypeptide) binding to four receptors in most mammals, namely the Y1, Y2, Y4 and Y5 receptors, with different affinity and selectivity3. NPY is the most powerful stimulant of food intake and this effect is primarily mediated by the Y1 receptor (Y1R)4. A number of peptides and small-molecule compounds have been characterized as Y1R antagonists and have shown clinical potential in the treatment of obesity4, tumour1 and bone loss5. However, their clinical usage has been hampered by low potency and selectivity, poor brain penetration ability or lack of oral bioavailability6. Here we report crystal structures of the human Y1R bound to the two selective antagonists UR-MK299 and BMS-193885 at 2.7 and 3.0 Å resolution, respectively. The structures combined with mutagenesis studies reveal the binding modes of Y1R to several structurally diverse antagonists and the determinants of ligand selectivity. The Y1R structure and molecular docking of the endogenous agonist NPY, together with nuclear magnetic resonance, photo-crosslinking and functional studies, provide insights into the binding behaviour of the agonist and for the first time, to our knowledge, determine the interaction of its N terminus with the receptor. These insights into Y1R can enable structure-based drug discovery that targets NPY receptors.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Fig. 1: Structures of the Y1R–UR-MK299 and Y1R–BMS-193885 complexes.
Fig. 2: Ligand-binding pocket in Y1R for UR-MK299 and BMS-193885.
Fig. 3: Inositol phosphate accumulation assays.
Fig. 4: Docking poses of NPY.


  1. 1.

    Zhang, L., Bijker, M. S. & Herzog, H. The neuropeptide Y system: pathophysiological and therapeutic implications in obesity and cancer. Pharmacol. Ther. 131, 91–113 (2011).

    CAS  Article  Google Scholar 

  2. 2.

    Morales-Medina, J. C., Dumont, Y. & Quirion, R. A possible role of neuropeptide Y in depression and stress. Brain Res. 1314, 194–205 (2010).

    CAS  Article  Google Scholar 

  3. 3.

    Michel, M. C. et al. XVI. International Union of Pharmacology recommendations for the nomenclature of neuropeptide Y, peptide YY, and pancreatic polypeptide receptors. Pharmacol. Rev. 50, 143–150 (1998).

    CAS  PubMed  Google Scholar 

  4. 4.

    Yulyaningsih, E., Zhang, L., Herzog, H. & Sainsbury, A. NPY receptors as potential targets for anti-obesity drug development. Br. J. Pharmacol. 163, 1170–1202 (2011).

    CAS  Article  Google Scholar 

  5. 5.

    Sousa, D. M., Herzog, H. & Lamghari, M. NPY signalling pathway in bone homeostasis: Y1 receptor as a potential drug target. Curr. Drug Targets 10, 9–19 (2009).

    CAS  Article  Google Scholar 

  6. 6.

    Antal-Zimanyi, I. et al. Pharmacological characterization and appetite suppressive properties of BMS-193885, a novel and selective neuropeptide Y1 receptor antagonist. Eur. J. Pharmacol. 590, 224–232 (2008).

    CAS  Article  Google Scholar 

  7. 7.

    Leibowitz, S. F., Sladek, C., Spencer, L. & Tempel, D. Neuropeptide Y, epinephrine and norepinephrine in the paraventricular nucleus: stimulation of feeding and the release of corticosterone, vasopressin and glucose. Brain Res. Bull. 21, 905–912 (1988).

    CAS  Article  Google Scholar 

  8. 8.

    MacNeil, D. J. NPY Y1 and Y5 receptor selective antagonists as anti-obesity drugs. Curr. Top. Med. Chem. 7, 1721–1733 (2007).

    CAS  Article  Google Scholar 

  9. 9.

    Reubi, J. C., Gugger, M., Waser, B. & Schaer, J. C. Y. Y1-mediated effect of neuropeptide Y in cancer: breast carcinomas as targets. Cancer Res. 61, 4636–4641 (2001).

    CAS  PubMed  Google Scholar 

  10. 10.

    Keller, M. et al. Nω-carbamoylation of the argininamide moiety: an avenue to insurmountable NPY Y1 receptor antagonists and a radiolabeled selective high-affinity molecular tool ([3H]UR-MK299) with extended residence time. J. Med. Chem. 58, 8834–8849 (2015).

    CAS  Article  Google Scholar 

  11. 11.

    White, J. F. et al. Structure of the agonist-bound neurotensin receptor. Nature 490, 508–513 (2012).

    ADS  CAS  Article  Google Scholar 

  12. 12.

    Yin, J. et al. Structure and ligand-binding mechanism of the human OX1 and OX2 orexin receptors. Nat. Struct. Mol. Biol. 23, 293–299 (2016).

    CAS  Article  Google Scholar 

  13. 13.

    Yin, J., Mobarec, J. C., Kolb, P. & Rosenbaum, D. M. Crystal structure of the human OX2 orexin receptor bound to the insomnia drug suvorexant. Nature 519, 247–250 (2015).

    ADS  CAS  Article  Google Scholar 

  14. 14.

    Shihoya, W. et al. Activation mechanism of endothelin ETB receptor by endothelin-1. Nature 537, 363–368 (2016).

    ADS  CAS  Article  Google Scholar 

  15. 15.

    Ballesteros, J. A. & Weinstein, H. in Methods in Neurosciences Vol. 25 (ed. S. Sealfon) 366–428 (Elsevier, Amsterdam, 1995).

  16. 16.

    Kaiser, A. et al. Unwinding of the C-terminal residues of neuropeptide Y is critical for Y2 receptor binding and activation. Angew. Chem. Int. Edn Engl. 54, 7446–7449 (2015).

    CAS  Article  Google Scholar 

  17. 17.

    Venkatakrishnan, A. J. et al. Molecular signatures of G-protein-coupled receptors. Nature 494, 185–194 (2013).

    ADS  CAS  Article  Google Scholar 

  18. 18.

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

    ADS  CAS  Article  Google Scholar 

  19. 19.

    Standfuss, J. et al. The structural basis of agonist-induced activation in constitutively active rhodopsin. Nature 471, 656–660 (2011).

    ADS  CAS  Article  Google Scholar 

  20. 20.

    Sautel, M. et al. Neuropeptide Y and the nonpeptide antagonist BIBP 3226 share an overlapping binding site at the human Y1 receptor. Mol. Pharmacol. 50, 285–292 (1996).

    CAS  PubMed  Google Scholar 

  21. 21.

    Keller, M. et al. Guanidine–acylguanidine bioisosteric approach in the design of radioligands: synthesis of a tritium-labeled N G-propionylargininamide ([3H]-UR-MK114) as a highly potent and selective neuropeptide Y Y1 receptor antagonist. J. Med. Chem. 51, 8168–8172 (2008).

    CAS  Article  Google Scholar 

  22. 22.

    Sjödin, P. et al. Re-evaluation of receptor-ligand interactions of the human neuropeptide Y receptor Y1: a site-directed mutagenesis study. Biochem. J. 393, 161–169 (2006).

    Article  Google Scholar 

  23. 23.

    Poindexter, G. S. et al. Dihydropyridine neuropeptide Y Y1 receptor antagonists. Bioorg. Med. Chem. Lett. 12, 379–382 (2002).

    CAS  Article  Google Scholar 

  24. 24.

    Poindexter, G. S. et al. Dihydropyridine neuropeptide Y Y1 receptor antagonists 2: bioisosteric urea replacements. Bioorg. Med. Chem. 12, 507–521 (2004).

    CAS  Article  Google Scholar 

  25. 25.

    Pedragosa-Badia, X., Stichel, J. & Beck-Sickinger, A. G. Neuropeptide Y receptors: how to get subtype selectivity. Front. Endocrinol. (Lausanne) 4, 5 (2013).

    CAS  Article  Google Scholar 

  26. 26.

    Bender, B. J. et al. Protocols for molecular modeling with Rosetta3 and RosettaScripts. Biochemistry 55, 4748–4763 (2016).

    CAS  Article  Google Scholar 

  27. 27.

    Merten, N. et al. Receptor subtype-specific docking of Asp6.59 with C-terminal arginine residues in Y receptor ligands. J. Biol. Chem. 282, 7543–7551 (2007).

    CAS  Article  Google Scholar 

  28. 28.

    Xu, B. et al. Mutagenesis and computational modeling of human G-protein-coupled receptor Y2 for neuropeptide Y and peptide YY. Biochemistry 52, 7987–7998 (2013).

    CAS  Article  Google Scholar 

  29. 29.

    Lindner, D., Walther, C., Tennemann, A. & Beck-Sickinger, A. G. Functional role of the extracellular N-terminal domain of neuropeptide Y subfamily receptors in membrane integration and agonist-stimulated internalization. Cell. Signal. 21, 61–68 (2009).

    CAS  Article  Google Scholar 

  30. 30.

    Laskowski, R. A. & Swindells, M. B. LigPlot+: multiple ligand-protein interaction diagrams for drug discovery. J. Chem. Inf. Model. 51, 2778–2786 (2011).

    CAS  Article  Google Scholar 

  31. 31.

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

    ADS  CAS  Article  Google Scholar 

  32. 32.

    Roth, C. B., Hanson, M. A. & Stevens, R. C. Stabilization of the human β2-adrenergic receptor TM4–TM3–TM5 helix interface by mutagenesis of Glu1223.41, a critical residue in GPCR structure. J. Mol. Biol. 376, 1305–1319 (2008).

    CAS  Article  Google Scholar 

  33. 33.

    Kabsch, W. XDS. Acta Crystallogr. D 66, 125–132 (2010).

    CAS  Article  Google Scholar 

  34. 34.

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

    CAS  Article  Google Scholar 

  35. 35.

    Murshudov, G. N. et al. REFMAC5 for the refinement of macromolecular crystal structures. Acta Crystallogr. D. 67, 355–367 (2011).

    CAS  Article  Google Scholar 

  36. 36.

    Smart, O. S. et al. Exploiting structure similarity in refinement: automated NCS and target-structure restraints in BUSTER. Acta Crystallogr. D. 68, 368–380 (2012).

    CAS  Article  Google Scholar 

  37. 37.

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

    CAS  Article  Google Scholar 

  38. 38.

    Keller, M. et al. Mimicking of arginine by functionalized N ω-carbamoylated arginine as a new broadly applicable approach to labeled bioactive peptides: high affinity angiotensin, neuropeptide Y, neuropeptide FF, and neurotensin receptor ligands as examples. J. Med. Chem. 59, 1925–1945 (2016).

    CAS  Article  Google Scholar 

  39. 39.

    Yung-Chi, C. & Prusoff, W. H. Relationship between the inhibition constant (K I) and the concentration of inhibitor which causes 50 per cent inhibition (I 50) of an enzymatic reaction. Biochem. Pharmacol. 22, 3099–3108 (1973).

    Article  Google Scholar 

  40. 40.

    Burkert, K. et al. A deep hydrophobic binding cavity is the main interaction for different Y2R antagonists. ChemMedChem. 12, 75–85 (2017).

    CAS  Article  Google Scholar 

  41. 41.

    Els, S., Beck-Sickinger, A. G. & Chollet, C. Ghrelin receptor: high constitutive activity and methods for developing inverse agonists. Methods Enzymol. 485, 103–121 (2010).

    CAS  Article  Google Scholar 

  42. 42.

    Kostenis, E. Is Gα16 the optimal tool for fishing ligands of orphan G-protein-coupled receptors? Trends Pharmacol. Sci. 22, 560–564 (2001).

    CAS  Article  Google Scholar 

  43. 43.

    Pedragosa-Badia, X. et al. Pancreatic polypeptide is recognized by two hydrophobic domains of the human Y4 receptor binding pocket. J. Biol. Chem. 289, 5846–5859 (2014).

    CAS  Article  Google Scholar 

  44. 44.

    Hoffmann, S., Rist, B., Videnov, G., Jung, G. & Beck-Sickinger, A. G. Structure-affinity studies of C-terminally modified analogs of neuropeptide Y led to a novel class of peptidic Y1 receptor antagonist. Regul. Pept. 65, 61–70 (1996).

    CAS  Article  Google Scholar 

  45. 45.

    Gerald, C. et al. A receptor subtype involved in neuropeptide-Y-induced food intake. Nature 382, 168–171 (1996).

    ADS  CAS  Article  Google Scholar 

  46. 46.

    Schmidt, P. et al. A reconstitution protocol for the in vitro folded human G protein-coupled Y2 receptor into lipid environment. Biophys. Chem. 150, 29–36 (2010).

    ADS  CAS  Article  Google Scholar 

  47. 47.

    Casiraghi, M. et al. Functional modulation of a G protein-coupled receptor conformational landscape in a lipid bilayer. J. Am. Chem. Soc. 138, 11170–11175 (2016).

    CAS  Article  Google Scholar 

  48. 48.

    Hohwy, M., Rienstra, C. M., Jaroniec, C. P. & Griffin, R. G. Fivefold symmetric homonuclear dipolar recoupling in rotating solids: application to double quantum spectroscopy. J. Chem. Phys. 110, 7983–7992 (1999).

    ADS  CAS  Article  Google Scholar 

  49. 49.

    Raveh, B., London, N., Zimmerman, L. & Schueler-Furman, O. Rosetta FlexPepDock ab-initio: simultaneous folding, docking and refinement of peptides onto their receptors. PLoS ONE 6, e18934 (2011).

    ADS  CAS  Article  Google Scholar 

  50. 50.

    Song, Y. et al. High-resolution comparative modeling with RosettaCM. Structure 21, 1735–1742 (2013).

    CAS  Article  Google Scholar 

  51. 51.

    Schwarz, D. et al. Preparative scale expression of membrane proteins in Escherichia coli-based continuous exchange cell-free systems. Nat. Protocols 2, 2945–2957 (2007).

    CAS  Article  Google Scholar 

  52. 52.

    Bosse, M. et al. Assessment of a fully active class A G protein-coupled receptor isolated from in vitro folding. Biochemistry 50, 9817–9825 (2011).

    CAS  Article  Google Scholar 

  53. 53.

    Wilkins, M. R. et al. Detailed peptide characterization using PEPTIDEMASS—a World-Wide-Web-accessible tool. Electrophoresis 18, 403–408 (1997).

    CAS  Article  Google Scholar 

Download references


We are grateful to T. Zellmann for his contribution to the modelling in the early state of the project and for the technical support of R. Reppich-Sacher (mass spectrometry) and K. Löbner (cell culture). We thank H. A. Scheidt for support with solid-state NMR measurements and M. Beer-Krön, D. Fritsch, S. Bollwein and B. Wenzl for expert help in performing radioligand-binding experiments. The synchrotron radiation experiments were performed at the BL41XU of SPring-8 with approval of the Japan Synchrotron Radiation Research Institute (proposal no. 2015B2026, 2015B2027, 2016A2517, 2016A2518, 2016B2517 and 2016B2518). We thank the beamline staff members K. Hasegawa, H. Okumura, N. Mizuno, T. Kawamura and H. Murakami of the BL41XU for help with X-ray data collection. This work was supported by CAS Strategic Priority Research Programs XDB08020000 (B.W.) and XDB08030102 (R.Z.), the Key Research Program of Frontier Sciences, CAS, Grant no. QYZDB-SSW-SMC024 (B.W.) and QYZDB-SSW-SMC054 (Q.Z.), the National Science Foundation of China grants 31570739 (B.W.), 81525024 (Q.Z.), 3170040264 (Z.Y.) and 31470792 (S.Y.), Program of Shanghai Academic/Technology Research Leader no. 18XD1404800 (Z.Y., Q.Z.), the European Community, the Free State of Saxony (SAB 100148835 to D.H. and 100881433 to A.G.B.-S.) and the Deutsche Forschungsgemeinschaft (DFG) (Be1264-16, SFB 1052/A3, research grant KE 1857/1-1 and Graduate Training Program GRK 1910). Work in the Meiler laboratory is supported by the NIH (R01 GM080403, R01 DK097376, R01 HL122010) and NSF (CHE 1305874).

Reviewer information

Nature thanks N. Holliday and the other anonymous reviewer(s) for their contribution to the peer review of this work.

Author information




Z.Y. and S.H. optimized the construct, developed the purification procedure, purified the Y1R protein for crystallization, performed crystallization trials, solved the structures and wrote the manuscript. M.K., D.W., G.B., N.P. and T.L. synthesized the compounds, designed, performed and analysed the ligand-binding assay. A.K., K.B. and L.M.K. performed peptide synthesis, inositol phosphate accumulation assays, the photo-crosslinking assay and mass spectrometry after crosslinking. B.J.B. helped to refine the Y1R–UR-MK299 structure and modelled the Y1R–NPY complex. M.B. and P.S. performed NMR analysis and analysed NMR data. C.Y. expressed the Y1R proteins. B.L. helped with construct and crystal optimization. S.Y., R.Z., B.X., D.L., R.C.S., D.H., J.M., A.G.B.-S. and A.B. helped with structure analysis, interpretation and edited the manuscript. R.C.S. helped to initiate the project. D.H. oversaw NMR studies. J.M. oversaw molecular docking. Q.Z. collected X-ray diffraction data and solved the structures. A.G.B.-S. oversaw peptide synthesis, inositol phosphate accumulation and photo-crosslinking assays. A.B. oversaw compound synthesis and ligand-binding assays. B.W. and Q.Z. initiated the project, planned and analysed experiments, supervised the research and wrote the manuscript with input from all co-authors.

Corresponding authors

Correspondence to Max Keller, Annette G. Beck-Sickinger or Beili Wu.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

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 Fig. 1 Crystal packing and structural features of Y1R and chemical structures of Y1R ligands.

a, b, Crystal packing of Y1R–UR-MK299 (a) and Y1R–BMS-193885 (b) complexes. Y1R is shown in cartoon representation and coloured brown and green in the Y1R–UR-MK299 and Y1R–BMS-193885 complexes, respectively. The T4L fusion is shown in grey cartoon representation. UR-MK299 and BMS-193885 are displayed as yellow and pink spheres, respectively. c, Cutaway view of the UR-MK299-binding pocket in Y1R. The receptor is shown in brown cartoon and surface representations. The ligand is shown as yellow sticks. d, Comparison of Y1R in the Y1R–UR-MK299 crystal structure (brown) and the Y1R–NPY model (green). Side chains of Q1203.32 and W2766.48 are shown as sticks. R35–Y36 of NPY is displayed as cyan sticks. The hydrogen bond between Q1203.32 and Y36 of NPY is shown as a green dashed line. ej, Chemical structures of the argininamide Y1R antagonists BIBP3226 (e), UR-HU404 (f), UR-MK299 (g), BIBO3304 (h), UR-MK289 (i) and UR-MK136 (j). k, Chemical structure of BMS-193885. l, Scaffold of NPY C-terminal residues R35 and Y36. Key differences between R35–Y36 of NPY and UR-MK299 are chirality of the arginine derivative and alteration of bond connectivity leading to the hydroxyphenyl group.

Extended Data Fig. 2 Expression of wild-type and mutant Y1 receptors in transiently transfected COS-7 cells.

a, Live-cell fluorescence microscopy verifies all Y1R variants to be properly folded and exported to the cell membrane like the wild-type receptor. Nuclei stained with Hoechst33342. Scale bars, 10 μm. Pictures are representative of two independent experiments with similar results. b, The total expression level was determined by fluorescence reading and expression was confirmed to be similar to the wild type. Transfection of only 50% or 25% of the DNA amount (with total DNA amount held constant by empty vector), led to a proportional decrease of fluorescence, and thus, expression level. Data represent mean ± s.e.m. of three to five independent experiments performed in technical triplicate (see Source Data for sample size of each mutant). c, Estimation of the receptor reserve in functional inositol phosphate accumulation assays. Transfection of half of the vector encoding the receptor (with a constant total DNA amount including chimeric G protein, see a) still produces maximum signal, while further reduction results in signal loss at comparable potency. Thus, there is only a small receptor reserve in the functional readout, allowing potency alteration to be directly related to compromised ligand binding. Data represent mean ± s.e.m. of three independent experiments performed in technical duplicate. cNPY, concentration of NPY.

Source data

Extended Data Fig. 3 Sequence alignment of the human NPY receptors and the human NPFF receptors.

Colours represent the similarity of residues: red background, identical; red text, strongly similar. Key residues in the UR-MK299-binding pocket, which are conserved or variable among receptors, are indicated by red or black arrows, respectively. The alignment was generated using UniProt ( and the graphic was prepared on the ESPript 3.0 server (

Extended Data Fig. 4 Pharmacological characterization of refolded Y1R and NMR studies of Y1R-bound NPY.

a, Binding of Atto 520-labelled NPY (50 nM) to increasing amounts of bicelles containing Y1R or empty bicelles. Data reflect fluorescence enhancement upon binding. An inflection point at EC50 = 52 nM was determined. Two independent experiments were performed in technical duplicate with similar results. Data shown are from a representative experiment. a.u., arbitrary units. c(Y1R), concentration of Y1R.  b, Typical 13C MAS single-quantum (SQ)/double-quantum (DQ) correlation spectrum of NPY in the presence of Y1R reconstituted into large bicelles at −30 °C. NMR spectra were acquired from one to three independent preparations for each labelled amino acid with similar results (see d). Data shown are from a representative experiment. c, Table showing 13C-NMR chemical shifts of assigned amino acids of NPY bound to Y1R (referenced to tetramethylsilane) as acquired in solid-state NMR experiments. d13C-chemical-shift index of NPY bound to Y1R in large DMPC/DHPC-c7 bicelles (q > 20) compared with docked models. Plotted in black is the measured chemical shift difference (Cα − Cβ) for each individual residue of NPY minus the chemical shift difference of the same amino acid type in random-coil conformation. Individual data points from one to three independent experiments for each labelled amino acid are shown. Typical experimental error when determining chemical shifts under these conditions are ± 1 p.p.m. Chemical shifts were back-calculated for the top docking solutions and filtered against the experimental data to generate a final ensemble of docked poses. Their average chemical-shift index and associated s.d. from the top ten docked poses are shown in red.

Extended Data Fig. 5 Photo-crosslinking experiments between NPY and Y1R.

a, Mass spectra of photo-crosslinked Y1R with [Bpa1, K4[(Ahx)2-biotin]]NPY. Exemplary MALDI–TOF mass spectra of photo-crosslinked samples enzymatically digested by rLys-C and Glu-C. Potential Y1R fragments are labelled. Two independent experiments were performed with similar results. N, N terminus of Y1R (blue); E, ECL2 (red). b, Respective regions of NPY N terminus at Y1R. Amino acid sequence of Y1R with a C-terminal His-tag. The two detected regions within Y1R (N terminus (blue), ECL2 (red)) after crosslinking with [Bpa1,K4[(Ahx)2-biotin]]NPY are emphasized in boxes. The different sizes of the boxes represent different detected fragments (Extended Data Table 5). Experiments were repeated twice independently with similar results, and only fragments that were observed in both experiments are listed here and in Extended Data Table 5. c, Binding of Atto 520-labelled NPY (50 nM) to increasing amounts of cell-free produced Y1R in Brij-58. Data reflect fluorescence enhancement upon binding. An EC50 value of 69 nM was determined. Data shown are mean ± s.e.m. from six independent experiments performed in technical triplicate. c(Y1R), concentration of Y1R.

Source data

Extended Data Table 1 Data collection and refinement statistics
Extended Data Table 2 Inositol phosphate accumulation assays of wild-type and mutant Y1 receptors for NPY and antagonists
Extended Data Table 3 Binding of Y1R antagonists and agonists to membrane preparations from Sf9 cells expressing wild-type and mutant Y1 receptors
Extended Data Table 4 Inositol phosphate accumulation assays of wild-type and mutant Y1 receptors for NPY and NPY analogues
Extended Data Table 5 Mass spectromeric signals and calculated mass of photo-crosslinked Y1R with [Bpa1, K4[(Ahx)2-biotin]]NPY

Supplementary information

Source data

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Yang, Z., Han, S., Keller, M. et al. Structural basis of ligand binding modes at the neuropeptide Y Y1 receptor. Nature 556, 520–524 (2018).

Download citation

Further reading


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.


Quick links