Structure of an endosomal signaling GPCR–G protein–β-arrestin megacomplex


Classically, G-protein-coupled receptors (GPCRs) are thought to activate G protein from the plasma membrane and are subsequently desensitized by β-arrestin (β-arr). However, some GPCRs continue to signal through G protein from internalized compartments, mediated by a GPCR–G protein–β-arr ‘megaplex’. Nevertheless, the molecular architecture of the megaplex remains unknown. Here, we present its cryo-electron microscopy structure, which shows simultaneous engagement of human G protein and bovine β-arr to the core and phosphorylated tail, respectively, of a single active human chimeric β2-adrenergic receptor with the C-terminal tail of the arginine vasopressin type 2 receptor (β2V2R). All three components adopt their canonical active conformations, suggesting that a single megaplex GPCR is capable of simultaneously activating G protein and β-arr. Our findings provide a structural basis for GPCR-mediated sustained internalized G protein signaling.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Fig. 1: Schematic illustration of the mechanism of sustained signaling through the formation of endosomal class B GPCR–G protein–β-arr megacomplexes.
Fig. 2: Cryo-EM structure of a β2V2R–Gs–β-arr1 megaplex.
Fig. 3: Structure and interactions of the β2V2R–Gs portion of the megaplex.
Fig. 4: Structure and interactions of the β-arr1–V2T portion of the megaplex.
Fig. 5: Comparison of the megaplex β-arr1–V2T to the V2Rpp–β-arr1–Fab30 and rhodopsin–visual arrestin crystal structures.
Fig. 6: The megaplex within a membrane environment.

Data availability

Cryo-EM maps corresponding to the consensus megaplex reconstruction as well as the signal-subtracted β2V2R–Gs and β-arr1–V2T subcomplexes have been deposited in the Electron Microscopy Data Bank (EMDB) with accession codes EMD-9377, EMD-9376 and EMD-9375, respectively. Atomic coordinates for the β2V2R–Gs and β-arr1–V2T subcomplexes have been deposited in the Protein Data Bank (PDB) with accession codes PDB 6NI3 and PDB 6NI2, respectively. The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD015298. Source data for Extended Data Figs. 1c and 1d are available with the paper online. Other data that support the findings of this study are available from the corresponding authors upon request.


  1. 1.

    Reiter, E., Ahn, S., Shukla, A. K. & Lefkowitz, R. J. Molecular mechanism of beta-arrestin-biased agonism at seven-transmembrane receptors. Annu. Rev. Pharmacol. Toxicol. 52, 179–197 (2012).

    CAS  PubMed  Google Scholar 

  2. 2.

    Lefkowitz, R. J., Stadel, J. M. & Caron, M. G. Adenylate cyclase-coupled beta-adrenergic receptors: structure and mechanisms of activation and desensitization. Annu. Rev. Biochem. 52, 159–186 (1983).

    CAS  PubMed  Google Scholar 

  3. 3.

    Rajagopal, S., Rajagopal, K. & Lefkowitz, R. J. Teaching old receptors new tricks: biasing seven-transmembrane receptors. Nat. Rev. Drug Discov. 9, 373–386 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  4. 4.

    Oakley, R. H., Laporte, S. A., Holt, J. A., Barak, L. S. & Caron, M. G. Association of beta-arrestin with G protein-coupled receptors during clathrin-mediated endocytosis dictates the profile of receptor resensitization. J. Biol. Chem. 274, 32248–32257 (1999).

    CAS  PubMed  Google Scholar 

  5. 5.

    Oakley, R. H., Laporte, S. A., Holt, J. A., Caron, M. G. & Barak, L. S. Differential affinities of visual arrestin, beta arrestin1, and beta arrestin2 for G protein-coupled receptors delineate two major classes of receptors. J. Biol. Chem. 275, 17201–17210 (2000).

    CAS  PubMed  Google Scholar 

  6. 6.

    Calebiro, D. et al. Persistent cAMP-signals triggered by internalized G-protein-coupled receptors. PLoS Biol. 7, e1000172 (2009).

    PubMed  PubMed Central  Google Scholar 

  7. 7.

    Ferrandon, S. et al. Sustained cyclic AMP production by parathyroid hormone receptor endocytosis. Nat. Chem. Biol. 5, 734–742 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  8. 8.

    Feinstein, T. N. et al. Noncanonical control of vasopressin receptor type 2 signaling by retromer and arrestin. J. Biol. Chem. 288, 27849–27860 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  9. 9.

    Thomsen, A. R. B. et al. GPCR-G Protein-beta-Arrestin Super-Complex Mediates Sustained G Protein Signaling. Cell 166, 907–919 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  10. 10.

    Shukla, A. K. et al. Visualization of arrestin recruitment by a G-protein-coupled receptor. Nature 512, 218–222 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  11. 11.

    Cahill, T. J. 3rd et al. Distinct conformations of GPCR-beta-arrestin complexes mediate desensitization, signaling, and endocytosis. Proc. Natl Acad. Sci. USA 114, 2562–2567 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  12. 12.

    Wehbi, V. L. et al. Noncanonical GPCR signaling arising from a PTH receptor-arrestin-Gbetagamma complex. Proc. Natl Acad. Sci. USA 110, 1530–1535 (2013).

    CAS  PubMed  Google Scholar 

  13. 13.

    Jimenez-Vargas, N. N. et al. Protease-activated receptor-2 in endosomes signals persistent pain of irritable bowel syndrome. Proc. Natl Acad. Sci. USA 115, E7438–E7447 (2018).

    CAS  PubMed  Google Scholar 

  14. 14.

    Wanka, L., Babilon, S., Kaiser, A., Morl, K. & Beck-Sickinger, A. G. Different mode of arrestin-3 binding at the human Y1 and Y2 receptor. Cell Signal 50, 58–71 (2018).

    CAS  PubMed  Google Scholar 

  15. 15.

    Rasmussen, S. G. et al. Crystal structure of the beta2 adrenergic receptor-Gs protein complex. Nature 477, 549–555 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  16. 16.

    Cherezov, V. et al. High-resolution crystal structure of an engineered human beta2-adrenergic G protein-coupled receptor. Science 318, 1258–1265 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  17. 17.

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

  18. 18.

    Ring, A. M. et al. Adrenaline-activated structure of beta2-adrenoceptor stabilized by an engineered nanobody. Nature 502, 575–579 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  19. 19.

    Rasmussen, S. G. et al. Structure of a nanobody-stabilized active state of the beta(2) adrenoceptor. Nature 469, 175–180 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  20. 20.

    Shukla, A. K. et al. Structure of active beta-arrestin-1 bound to a G-protein-coupled receptor phosphopeptide. Nature 497, 137–141 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  21. 21.

    Fredericks, Z. L., Pitcher, J. A. & Lefkowitz, R. J. Identification of the G protein-coupled receptor kinase phosphorylation sites in the human beta2-adrenergic receptor. J. Biol. Chem. 271, 13796–13803 (1996).

    CAS  PubMed  Google Scholar 

  22. 22.

    Lally, C. C., Bauer, B., Selent, J. & Sommer, M. E. C-edge loops of arrestin function as a membrane anchor. Nat. Commun. 8, 14258 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  23. 23.

    Zhou, X. E. et al. Identification of Phosphorylation Codes for Arrestin Recruitment by G Protein-Coupled Receptors. Cell 170, 457–469 (2017). e13.

    CAS  PubMed  PubMed Central  Google Scholar 

  24. 24.

    Lohse, M. J., Benovic, J. L., Codina, J., Caron, M. G. & Lefkowitz, R. J. beta-Arrestin: a protein that regulates beta-adrenergic receptor function. Science 248, 1547–1550 (1990).

    CAS  PubMed  Google Scholar 

  25. 25.

    Lohse, M. J. et al. Receptor-specific desensitization with purified proteins. Kinase dependence and receptor specificity of beta-arrestin and arrestin in the beta 2-adrenergic receptor and rhodopsin systems. J. Biol. Chem. 267, 8558–8564 (1992).

    CAS  PubMed  Google Scholar 

  26. 26.

    Kang, Y. et al. Crystal structure of rhodopsin bound to arrestin by femtosecond X-ray laser. Nature 523, 561–567 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  27. 27.

    Liang, Y. L. et al. Phase-plate cryo-EM structure of a class B GPCR-G-protein complex. Nature 546, 118–123 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  28. 28.

    Zhang, Y. et al. Cryo-EM structure of the activated GLP-1 receptor in complex with a G protein. Nature 546, 248–253 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  29. 29.

    Le Gouill, C., Innamorati, G. & Birnbaumer, M. An expanded V2 receptor retention signal. FEBS Lett. 532, 363–366 (2002).

    PubMed  Google Scholar 

  30. 30.

    Innamorati, G., Sadeghi, H. M., Tran, N. T. & Birnbaumer, M. A serine cluster prevents recycling of the V2 vasopressin receptor. Proc. Natl Acad. Sci. USA 95, 2222–2226 (1998).

    CAS  PubMed  Google Scholar 

  31. 31.

    Mayer, D. et al. Distinct G protein-coupled receptor phosphorylation motifs modulate arrestin affinity and activation and global conformation. Nat. Commun. 10, 1261 (2019).

    PubMed  PubMed Central  Google Scholar 

  32. 32.

    Liang, Y. L. et al. Cryo-EM structure of the active, Gs-protein complexed, human CGRP receptor. Nature 561, 492–497 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  33. 33.

    Liang, Y. L. et al. Phase-plate cryo-EM structure of a biased agonist-bound human GLP-1 receptor-Gs complex. Nature 555, 121–125 (2018).

    CAS  PubMed  Google Scholar 

  34. 34.

    Irannejad, R. et al. Conformational biosensors reveal GPCR signalling from endosomes. Nature 495, 534–538 (2013).

    CAS  PubMed  Google Scholar 

  35. 35.

    Yang, M., He, R. L., Benovic, J. L. & Ye, R. D. beta-Arrestin1 interacts with the G-protein subunits beta1gamma2 and promotes beta1gamma2-dependent Akt signalling for NF-kappaB activation. Biochem. J. 417, 287–296 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  36. 36.

    Gaudet, R., Bohm, A. & Sigler, P. B. Crystal structure at 2.4 angstroms resolution of the complex of transducin betagamma and its regulator, phosducin. Cell 87, 577–588 (1996).

    CAS  PubMed  Google Scholar 

  37. 37.

    Lodowski, D. T., Pitcher, J. A., Capel, W. D., Lefkowitz, R. J. & Tesmer, J. J. Keeping G proteins at bay: a complex between G protein-coupled receptor kinase 2 and Gbetagamma. Science 300, 1256–1262 (2003).

    CAS  PubMed  Google Scholar 

  38. 38.

    Whorton, M. R. & MacKinnon, R. X-ray structure of the mammalian GIRK2-betagamma G-protein complex. Nature 498, 190–197 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  39. 39.

    Noble, A. J. et al. Routine single particle CryoEM sample and grid characterization by tomography. eLife 7, e34257 (2018).

    PubMed  PubMed Central  Google Scholar 

  40. 40.

    Mastronarde, D. N. Automated electron microscope tomography using robust prediction of specimen movements. J. Struct. Biol. 152, 36–51 (2005).

    Google Scholar 

  41. 41.

    Tan, Y. Z. et al. Addressing preferred specimen orientation in single-particle cryo-EM through tilting. Nat. Methods 14, 793–796 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  42. 42.

    Suloway, C. et al. Automated molecular microscopy: the new Leginon system. J. Struct. Biol. 151, 41–60 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  43. 43.

    Tegunov, D. & Cramer, P. Real-time cryo-electron microscopy data preprocessing with Warp. Nat. Methods 16, 1146–1152 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  44. 44.

    Zivanov, J. et al. New tools for automated high-resolution cryo-EM structure determination in RELION-3. eLife 7, e42166 (2018).

    PubMed  PubMed Central  Google Scholar 

  45. 45.

    Punjani, A., Rubinstein, J. L., Fleet, D. J. & Brubaker, M. A. cryoSPARC: algorithms for rapid unsupervised cryo-EM structure determination. Nat. Methods 14, 290–296 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  46. 46.

    Vilas, J. L. et al. MonoRes: Automatic and Accurate Estimation of Local Resolution for Electron Microscopy Maps. Structure 26, 337–344 (2018). e4.

    CAS  PubMed  Google Scholar 

  47. 47.

    Adams, P. D. et al. PHENIX: a comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr. D Biol. Crystallogr. 6, 213–221 (2010).

    Google Scholar 

  48. 48.

    Roy, A., Kucukural, A. & Zhang, Y. I-TASSER: a unified platform for automated protein structure and function prediction. Nat. Protoc. 5, 725–738 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  49. 49.

    Pettersen, E. F. et al. UCSF Chimera–a visualization system for exploratory research and analysis. J. Comput. Chem. 25, 1605–1612 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  50. 50.

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

    CAS  PubMed  PubMed Central  Google Scholar 

  51. 51.

    Chen, V. B. et al. MolProbity: all-atom structure validation for macromolecular crystallography. Acta Crystallogr. D Biol. Crystallogr. 66, 12–21 (2010).

    CAS  Google Scholar 

  52. 52.

    Goddard, T. D. et al. UCSF ChimeraX: Meeting modern challenges in visualization and analysis. Protein Sci. 27, 14–25 (2018).

    CAS  PubMed  Google Scholar 

  53. 53.

    Marrink, S. J. & Mark, A. E. Molecular view of hexagonal phase formation in phospholipid membranes. Biophys. J. 87, 3894–3900 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  54. 54.

    Jo, S., Kim, T., Iyer, V. G. & Im, W. CHARMM-GUI: a web-based graphical user interface for CHARMM. J. Comput. Chem. 29, 1859–1865 (2008).

    CAS  PubMed  Google Scholar 

  55. 55.

    Pronk, S. et al. GROMACS 4.5: a high-throughput and highly parallel open source molecular simulation toolkit. Bioinformatics 29, 845–854 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  56. 56.

    Humphrey, W., Dalke, A. & Schulten, K. VMD: visual molecular dynamics. J. Mol. Graph. 14, 27–28 (1996).

    Google Scholar 

  57. 57.

    Shevchenko, A., Tomas, H., Havlis, J., Olsen, J. V. & Mann, M. In-gel digestion for mass spectrometric characterization of proteins and proteomes. Nat. Protoc. 1, 2856–2860 (2006).

    CAS  PubMed  Google Scholar 

  58. 58.

    Cox, J. & Mann, M. MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification. Nat. Biotechnol. 26, 1367–1372 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  59. 59.

    Olsen, J. V. & Mann, M. Improved peptide identification in proteomics by two consecutive stages of mass spectrometric fragmentation. Proc. Natl Acad. Sci. USA 101, 13417–13422 (2004).

    CAS  PubMed  Google Scholar 

  60. 60.

    MacLean, B. et al. Skyline: an open source document editor for creating and analyzing targeted proteomics experiments. Bioinformatics 26, 966–968 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

Download references


We thank Q. Lennon, J. Bisson and J. Taylor for excellent administrative support, W. Capel for technical support, Y. Zhang and G. Skiniotis for help with initial sample screening, C.-R. Liang, L.-L. Gu and J.-M. Shan for synthesizing BI-167107, T. Wang and the CUNY Advanced Science Research Center Imaging Facility for help with sample screening and data collection, the lab of K. Gardner at the CUNY Advanced Science Research Center for providing various general lab reagents and equipment during initial sample screening, M. Walters, M. DeLong, M. Plue, T. Milledge, D. Capel and X. Jiang at Duke University for technical support and discussion, D. Lyumkis, D. Tegunov, W. Rice, E. Eng, L. Kim, M. Kopylov and A. Cheng for help with tilted data collection and processing and S. Houston and B. Plouffe for helpful discussion. This work received support from NIH grants (nos. T32GM007171 and F30HL149213 to A.H.N; F30HL129803 to T.J.C.; T32GM007767 to J.P.M.; R35GM133598 to A.d.G. and R01HL016037 to R.J.L.); HHMI Medical Research Fellowship to A.H.N.; the Danish Council for Independent Research & Lundbeck Foundation (DFF-5053-00136 and R172-2014-1468 to A.R.B.T.); American Heart Association Innovative Project Award (no. 19IPLOI34760706 to A.d.G); Institut de Recherche Servier (no. 18021932 to A.d.G. and D.B.-H.); and American Heart Association Predoctoral Fellowship (no. 13PRE17110027 to J.P.M.). Some of this work was performed at the Simons Electron Microscopy Center and National Resource for Automated Molecular Microscopy located at the New York Structural Biology Center, supported by grants from the Simons Foundation (grant no. SF349247), NYSTAR, and the NIH National Institute of General Medical Sciences (grant no. GM103310) with additional support from Agouron Institute (grant no. F00316) and the NIH (grant no. OD019994). R.J.L. is an HHMI Investigator.

Author information




A.H.N., A.R.B.T., T.J.C. III, A.d.G. and R.J.L. conceived the project and designed experimental approaches. A.H.N., A.R.B.T., T.J.C. III, L.-Y.H., A.M., J.P.M., J.L. IV and R.S. purified protein for cryo-EM structural determination. A.H.N. prepared cryo-EM samples with contributions from V.P.D. A.H.N., A.R.B.T., T.J.C. III, D.B.-H., F.S. and A.d.G. performed initial sample screenings. R.H. and Z.Y. performed cryo-EM imaging with contributions from C.H. A.H.N. processed cryo-EM data with input from A.d.G. and Y.Z.T. A.H.N. and O.B.C. built the atomic models. S.T. and J.S. raised nanobody 32 and X.C. synthesized BI-167107. S.H. and H.M. performed LC–MS/MS experiments and data analyses. T.M. performed coarse-grained molecular dynamics analysis. A.R.B.T. performed real-time cellular cAMP measurement experiments. A.H.N., A.R.B.T., T.J.C. III, A.d.G. and R.J.L. interpreted the data and wrote the manuscript. R.J.L. and A.d.G. were responsible for project supervision and management.

Corresponding authors

Correspondence to Amedee des Georges or Robert J. Lefkowitz.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Peer review information Katarzyna Marcinkiewicz was the primary editor on this article and managed its editorial process and peer review in collaboration with the rest of the editorial team.

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

Extended data

Extended Data Fig. 1 Sample preparation and purification of the megaplex.

a, Schematic illustration of the purification and in vitro formation procedure of the megaplex. b, Size exclusion chromatogram of the precursor β2V2R–βarr1–Fab30 complex. c, SDS-PAGE gel of the β2V2R–βarr1–Fab30 complex after purification by size exclusion chromatography. d, SDS-PAGE gel of the megaplex after in vitro formation and M1 anti-Flag purification. For c-d, M denotes molecular weight (kDa) marker. Uncropped gel images for Extended Data Fig. 1c,d are provided as Source Data. Source data

Extended Data Fig. 2 Nanobody 32 (Nb32) stabilizes the megaplex.

a, Representative micrograph and 2D class averages of megaplex samples prepared without nanobody 32 (Nb32), displaying a small percentage of megaplexes. b, Same as in a, but with a megaplex sample prepared with Nb32.

Extended Data Fig. 3 A procedure utilizing Warp and cryoSPARC for initial data processing and cleaning of one representative dataset (Dataset 2).

The same procedure was used on all dataset.

Extended Data Fig. 4

Data processing workflow for all datasets of the megaplex.

Extended Data Fig. 5 Megaplex consensus reconstruction.

a, Representative 2D class averages of the consensus megaplex reconstruction. b-c, The megaplex reconstruction is shown at high (0.115) threshold (b), and low (0.05) threshold (c). The T4L and flexible portion of the V2T appears at a lower threshold. The atomic models of the components, derived from signal subtracted reconstructions, are fitted to the consensus reconstruction. Densities for the flexible V2T and steric clash between the β2V2R and Nb32 are denoted by black circles.

Extended Data Fig. 6 Orientational distribution and resolution measurements of the megaplex.

a–d, orientational distribution (a), FSC curves indicating overall resolution (FSC = 0.143) (b), 3D-FSC to assess directional resolution anisotropy (c), and local resolution measurements (d) of the megaplex consensus reconstruction. e–j, orientational distribution (e), FSC curves indicating overall resolution (FSC = 0.143) (f), 3D-FSC to assess directional resolution anisotropy (g), map-to-model FSC and sphericity (h), local resolution measurements (i), and map-to-model FSC curve (j) of the β2V2R–Gs reconstruction. k–p, same as e–j, but for the βarr1–V2T reconstruction.

Extended Data Fig. 7 Representative densities in black mesh of various protein components.

Representative densities, from the 3.8 Å β2V2R–Gs and 4.0 Å βarr1–V2T structures, of the β2V2R, Gs subunits, and βarr1.

Extended Data Fig. 8 Representative density of the β2V2R–Gs portion of the megaplex, and comparison against other active β2AR structures.

a, Comparison of the binding pose of BI-167107 (BI) in the megaplex against three other available BI-bound β2AR structures. BI is colored green. b, Representative density showing contacts between the β2V2R and Gs in the megaplex. c, The BI binding pocket within the megaplex, accompanied by EM density for all residues within 5 Å of the ligand.

Extended Data Fig. 9 Interaction between Fab30, V2T and protein stabilizers.

a, b, Interface between βarr1 and V2T with either Nb32 (a) or Fab30 (b). Interface residues are labeled.

Extended Data Fig. 10 Verification of observed phosphorylation sites on the V2T.

a, Cryo-EM density for the six phosphorylated residues on the V2T. b, Localization probabilities of eight potential sites of phosphorylation on the V2T assessed by LC-MS/MS. A trypsin-digested fragment of the V2T is displayed. Bolded residues are phosphorylation sites observed in the cryo-EM map. Residues in red were not observed in the map, and yellow-highlighted residues were phosphorylated in both unstimulated and BI-stimulated receptors.

Supplementary information

Source data

Source Data Extended Data Fig. 1

Uncropped Coomassie-stained reducing SDS-PAGE gels of Extended Data Figure 1c,d.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Nguyen, A.H., Thomsen, A.R.B., Cahill, T.J. et al. Structure of an endosomal signaling GPCR–G protein–β-arrestin megacomplex. Nat Struct Mol Biol 26, 1123–1131 (2019).

Download citation

Further reading


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