{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T02:49:29Z","timestamp":1792118969029,"version":"4.4.0"},"reference-count":47,"publisher":"Springer Science and Business Media LLC","issue":"7398","license":[{"start":{"date-parts":[[2012,3,21]],"date-time":"2012-03-21T00:00:00Z","timestamp":1332288000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nature"],"published-print":{"date-parts":[[2012,5]]},"DOI":"10.1038\/nature10954","type":"journal-article","created":{"date-parts":[[2012,3,20]],"date-time":"2012-03-20T08:21:18Z","timestamp":1332231678000},"page":"321-326","source":"Crossref","is-referenced-by-count":1300,"title":["Crystal structure of the \u00b5-opioid receptor bound to a morphinan antagonist"],"prefix":"10.1038","volume":"485","author":[{"given":"Aashish","family":"Manglik","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew C.","family":"Kruse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tong Sun","family":"Kobilka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Foon Sun","family":"Thian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesper M.","family":"Mathiesen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger K.","family":"Sunahara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonardo","family":"Pardo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William I.","family":"Weis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian K.","family":"Kobilka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e9bastien","family":"Granier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2012,3,21]]},"reference":[{"key":"BFnature10954_CR1","volume-title":"Basic and Clinical Pharmacology","author":"BG Katzung","year":"2007","unstructured":"Katzung, B. G. Basic and Clinical Pharmacology 10th edn (LANGE McGraw Hill Medical, 2007)"},{"key":"BFnature10954_CR2","doi-asserted-by":"publisher","first-page":"819","DOI":"10.1038\/383819a0","volume":"383","author":"HW Matthes","year":"1996","unstructured":"Matthes, H. W. et al. Loss of morphine-induced analgesia, reward effect and withdrawal symptoms in mice lacking the \u03bc-opioid-receptor gene. Nature 383, 819\u2013823 (1996)","journal-title":"Nature"},{"key":"BFnature10954_CR3","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1038\/267495a0","volume":"267","author":"JA Lord","year":"1977","unstructured":"Lord, J. A., Waterfield, A. A., Hughes, J. & Kosterlitz, H. W. Endogenous opioid peptides: multiple agonists and receptors. Nature 267, 495\u2013499 (1977)","journal-title":"Nature"},{"key":"BFnature10954_CR4","doi-asserted-by":"publisher","first-page":"R5","DOI":"10.1016\/0014-2999(94)90073-6","volume":"258","author":"RB Raffa","year":"1994","unstructured":"Raffa, R. B., Martinez, R. P. & Connelly, C. D. G-protein antisense oligodeoxyribonucleotides and \u03bc-opioid supraspinal antinociception. Eur. J. Pharmacol. 258, R5\u2013R7 (1994)","journal-title":"Eur. J. Pharmacol."},{"key":"BFnature10954_CR5","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1016\/j.tibs.2011.06.003","volume":"36","author":"AK Shukla","year":"2011","unstructured":"Shukla, A. K., Xiao, K. & Lefkowitz, R. J. Emerging paradigms of \u03b2-arrestin-dependent seven transmembrane receptor signaling. Trends Biochem. Sci. 36, 457\u2013469 (2011)","journal-title":"Trends Biochem. Sci."},{"key":"BFnature10954_CR6","doi-asserted-by":"publisher","first-page":"12522","DOI":"10.1074\/jbc.M109.059410","volume":"285","author":"P Molinari","year":"2010","unstructured":"Molinari, P. et al. Morphine-like opiates selectively antagonize receptor-arrestin interactions. J. Biol. Chem. 285, 12522\u201312535 (2010)","journal-title":"J. Biol. Chem."},{"key":"BFnature10954_CR7","doi-asserted-by":"publisher","first-page":"1266","DOI":"10.1126\/science.1150609","volume":"318","author":"DM Rosenbaum","year":"2007","unstructured":"Rosenbaum, D. M. et al. GPCR engineering yields high-resolution structural insights into \u03b22-adrenergic receptor function. Science 318, 1266\u20131273 (2007)","journal-title":"Science"},{"key":"BFnature10954_CR8","first-page":"366","volume":"25","author":"JA Ballesteros","year":"1995","unstructured":"Ballesteros, J. A. & Weinstein, H. Integrated Methods for the Construction of Three Dimensional Models and Computational Probing of Structure Function Relations in G Protein-Coupled Receptors Vol. 25 366\u2013428 (Academic, 1995)","journal-title":"Integrated Methods for the Construction of Three Dimensional Models and Computational Probing of Structure Function Relations in G Protein-Coupled Receptors"},{"key":"BFnature10954_CR9","doi-asserted-by":"publisher","first-page":"21422","DOI":"10.1074\/jbc.271.35.21422","volume":"271","author":"C Chen","year":"1996","unstructured":"Chen, C. et al. Determination of the amino acid residue involved in [3H]\u03b2-funaltrexamine covalent binding in the cloned rat \u03bc-opioid receptor. J. Biol. Chem. 271, 21422\u201321429 (1996)","journal-title":"J. Biol. Chem."},{"key":"BFnature10954_CR10","doi-asserted-by":"publisher","first-page":"13501","DOI":"10.1021\/bi010917q","volume":"40","author":"P Huang","year":"2001","unstructured":"Huang, P. et al. Functional role of a conserved motif in TM6 of the rat \u03bc opioid receptor: constitutively active and inactive receptors result from substitutions of Thr6.34(279) with Lys and Asp. Biochemistry 40, 13501\u201313509 (2001)","journal-title":"Biochemistry"},{"key":"BFnature10954_CR11","doi-asserted-by":"publisher","first-page":"547","DOI":"10.1038\/nature10753","volume":"482","author":"K Haga","year":"2012","unstructured":"Haga, K. et al. Structure of the human M2 muscarinic acetylcholine receptor bound to an antagonist. Nature 482, 547\u2013551 (2012)","journal-title":"Nature"},{"key":"BFnature10954_CR12","doi-asserted-by":"publisher","first-page":"552","DOI":"10.1038\/nature10867","volume":"482","author":"AC Kruse","year":"2012","unstructured":"Kruse, A. C. et al. Structure and dynamics of the M3 muscarinic acetylcholine receptor. Nature 482, 552\u2013556 (2012)","journal-title":"Nature"},{"key":"BFnature10954_CR13","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1016\/0024-3205(93)90312-Q","volume":"52","author":"B Disse","year":"1993","unstructured":"Disse, B. et al. Ba 679 BR, a novel long-acting anticholinergic bronchodilator. Life Sci. 52, 537\u2013544 (1993)","journal-title":"Life Sci."},{"key":"BFnature10954_CR14","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/j.ejphar.2005.08.008","volume":"520","author":"JA Cassel","year":"2005","unstructured":"Cassel, J. A., Daubert, J. D. & DeHaven, R. N. [3H]Alvimopan binding to the \u03bc opioid receptor: comparative binding kinetics of opioid antagonists. Eur. J. Pharmacol. 520, 29\u201336 (2005)","journal-title":"Eur. J. Pharmacol."},{"key":"BFnature10954_CR15","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1016\/0006-8993(82)90068-3","volume":"249","author":"M Kurowski","year":"1982","unstructured":"Kurowski, M., Rosenbaum, J. S., Perry, D. C. & Sadee, W. [3H]-etorphine and [3H]-diprenorphine receptor binding in vitro and in vivo: differential effect of Na+ and guanylyl imidodiphosphate. Brain Res. 249, 345\u2013352 (1982)","journal-title":"Brain Res."},{"key":"BFnature10954_CR16","doi-asserted-by":"publisher","first-page":"584","DOI":"10.7326\/0003-4819-130-7-199904060-00019","volume":"130","author":"KA Sporer","year":"1999","unstructured":"Sporer, K. A. Acute heroin overdose. Ann. Intern. Med. 130, 584\u2013590 (1999)","journal-title":"Ann. Intern. Med."},{"key":"BFnature10954_CR17","first-page":"702","volume":"164","author":"BT Alford","year":"1974","unstructured":"Alford, B. T., Burkhart, R. L. & Johnson, W. P. Etorphine and diprenorphine as immobilizing and reversing agents in captive and free-ranging mammals. J. Am. Vet. Med. Assoc. 164, 702\u2013705 (1974)","journal-title":"J. Am. Vet. Med. Assoc."},{"key":"BFnature10954_CR18","doi-asserted-by":"publisher","first-page":"1066","DOI":"10.1126\/science.1194396","volume":"330","author":"B Wu","year":"2010","unstructured":"Wu, B. et al. Structures of the CXCR4 chemokine GPCR with small-molecule and cyclic peptide antagonists. Science 330, 1066\u20131071 (2010)","journal-title":"Science"},{"key":"BFnature10954_CR19","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1046\/j.1471-4159.1997.68010344.x","volume":"68","author":"A Mansour","year":"1997","unstructured":"Mansour, A. et al. Key residues defining the \u03bc-opioid receptor binding pocket: a site-directed mutagenesis study. J. Neurochem. 68, 344\u2013353 (1997)","journal-title":"J. Neurochem."},{"key":"BFnature10954_CR20","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/S0014-2999(00)00578-1","volume":"403","author":"G Bonner","year":"2000","unstructured":"Bonner, G., Meng, F. & Akil, H. Selectivity of \u03bc-opioid receptor determined by interfacial residues near third extracellular loop. Eur. J. Pharmacol. 403, 37\u201344 (2000)","journal-title":"Eur. J. Pharmacol."},{"key":"BFnature10954_CR21","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1038\/386499a0","volume":"386","author":"JE Zadina","year":"1997","unstructured":"Zadina, J. E., Hackler, L., Ge, L. J. & Kastin, A. J. A potent and selective endogenous agonist for the \u03bc-opiate receptor. Nature 386, 499\u2013502 (1997)","journal-title":"Nature"},{"key":"BFnature10954_CR22","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1016\/S0014-2999(98)00240-4","volume":"350","author":"T Seki","year":"1998","unstructured":"Seki, T. et al. DAMGO recognizes four residues in the third extracellular loop to discriminate between \u03bc- and \u03ba-opioid receptors. Eur. J. Pharmacol. 350, 301\u2013310 (1998)","journal-title":"Eur. J. Pharmacol."},{"key":"BFnature10954_CR23","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1007\/978-1-60761-993-2_15","volume":"23","author":"R Rozenfeld","year":"2011","unstructured":"Rozenfeld, R., Gomes, I. & Devi, L. in The Opiate Receptors Vol. 23 (ed. Pasternak, G. W. ) Ch. 15 407\u2013437 (Humana, 2011)","journal-title":"The Opiate Receptors"},{"key":"BFnature10954_CR24","doi-asserted-by":"publisher","first-page":"1682","DOI":"10.1021\/bi101474v","volume":"50","author":"JM Johnston","year":"2011","unstructured":"Johnston, J. M. et al. Making structural sense of dimerization interfaces of \u03b4 opioid receptor homodimers. Biochemistry 50, 1682\u20131690 (2011)","journal-title":"Biochemistry"},{"key":"BFnature10954_CR25","doi-asserted-by":"publisher","first-page":"PR438","DOI":"10.1021\/cr100437t","volume":"111","author":"F Fanelli","year":"2011","unstructured":"Fanelli, F. & De Benedetti, P. G. Update 1 of: computational modeling approaches to structure-function analysis of G protein-coupled receptors. Chem. Rev. 111, PR438\u2013PR535 (2011)","journal-title":"Chem. Rev."},{"key":"BFnature10954_CR26","doi-asserted-by":"publisher","first-page":"16384","DOI":"10.1074\/jbc.271.27.16384","volume":"271","author":"TE Hebert","year":"1996","unstructured":"Hebert, T. E. et al. A peptide derived from a \u03b22-adrenergic receptor transmembrane domain inhibits both receptor dimerization and activation. J. Biol. Chem. 271, 16384\u201316392 (1996)","journal-title":"J. Biol. Chem."},{"key":"BFnature10954_CR27","doi-asserted-by":"publisher","first-page":"50904","DOI":"10.1074\/jbc.M405089200","volume":"279","author":"S Granier","year":"2004","unstructured":"Granier, S. et al. A cyclic peptide mimicking the third intracellular loop of the V2 vasopressin receptor inhibits signaling through its interaction with receptor dimer and G protein. J. Biol. Chem. 279, 50904\u201350914 (2004)","journal-title":"J. Biol. Chem."},{"key":"BFnature10954_CR28","doi-asserted-by":"publisher","first-page":"604","DOI":"10.1096\/fj.11-191510","volume":"26","author":"J Hu","year":"2011","unstructured":"Hu, J. et al. Structural aspects of M3 muscarinic acetylcholine receptor dimer formation and activation. FASEB J. 26, 604\u2013616 (2011)","journal-title":"FASEB J."},{"key":"BFnature10954_CR29","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1038\/nature07063","volume":"454","author":"JH Park","year":"2008","unstructured":"Park, J. H., Scheerer, P., Hofmann, K. P., Choe, H. W. & Ernst, O. P. Crystal structure of the ligand-free G-protein-coupled receptor opsin. Nature 454, 183\u2013187 (2008)","journal-title":"Nature"},{"key":"BFnature10954_CR30","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1016\/j.neuron.2010.12.001","volume":"69","author":"SQ He","year":"2011","unstructured":"He, S. Q. et al. Facilitation of \u03bc-opioid receptor activity by preventing \u03b4-opioid receptor-mediated codegradation. Neuron 69, 120\u2013131 (2011)","journal-title":"Neuron"},{"key":"BFnature10954_CR31","doi-asserted-by":"publisher","first-page":"697","DOI":"10.1038\/21441","volume":"399","author":"BA Jordan","year":"1999","unstructured":"Jordan, B. A. & Devi, L. A. G-protein-coupled receptor heterodimerization modulates receptor function. Nature 399, 697\u2013700 (1999)","journal-title":"Nature"},{"key":"BFnature10954_CR32","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1016\/S0092-8674(02)00613-X","volume":"108","author":"L He","year":"2002","unstructured":"He, L., Fong, J., von Zastrow, M. & Whistler, J. L. Regulation of opioid receptor trafficking and morphine tolerance by receptor oligomerization. Cell 108, 271\u2013282 (2002)","journal-title":"Cell"},{"key":"BFnature10954_CR33","doi-asserted-by":"publisher","first-page":"1028","DOI":"10.1016\/j.cub.2005.04.052","volume":"15","author":"L He","year":"2005","unstructured":"He, L. & Whistler, J. L. An opiate cocktail that reduces morphine tolerance and dependence. Curr. Biol. 15, 1028\u20131033 (2005)","journal-title":"Curr. Biol."},{"key":"BFnature10954_CR34","doi-asserted-by":"publisher","first-page":"26128","DOI":"10.1074\/jbc.M000345200","volume":"275","author":"SR George","year":"2000","unstructured":"George, S. R. et al. Oligomerization of \u03bc- and \u03b4-opioid receptors. Generation of novel functional properties. J. Biol. Chem. 275, 26128\u201326135 (2000)","journal-title":"J. Biol. Chem."},{"key":"BFnature10954_CR35","doi-asserted-by":"publisher","first-page":"1044","DOI":"10.1124\/mol.110.070847","volume":"79","author":"I Gomes","year":"2011","unstructured":"Gomes, I., Ijzerman, A. P., Ye, K., Maillet, E. L. & Devi, L. A. G protein-coupled receptor heteromerization: a role in allosteric modulation of ligand binding. Mol. Pharmacol. 79, 1044\u20131052 (2011)","journal-title":"Mol. Pharmacol."},{"key":"BFnature10954_CR36","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1038\/nchembio.64","volume":"4","author":"JP Vilardaga","year":"2008","unstructured":"Vilardaga, J. P. et al. Conformational cross-talk between \u03b12A-adrenergic and \u03bc-opioid receptors controls cell signaling. Nature Chem. Biol. 4, 126\u2013131 (2008)","journal-title":"Nature Chem. Biol."},{"key":"BFnature10954_CR37","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1038\/nature10361","volume":"477","author":"SG Rasmussen","year":"2011","unstructured":"Rasmussen, S. G. et al. Crystal structure of the \u03b22 adrenergic receptor\u2013Gs protein complex. Nature 477, 549\u2013555 (2011)","journal-title":"Nature"},{"key":"BFnature10954_CR38","doi-asserted-by":"publisher","first-page":"3315","DOI":"10.1038\/emboj.2009.267","volume":"28","author":"JJ Fung","year":"2009","unstructured":"Fung, J. J. et al. Ligand-regulated oligomerization of \u03b22-adrenoceptors in a model lipid bilayer. EMBO J. 28, 3315\u20133328 (2009)","journal-title":"EMBO J."},{"key":"BFnature10954_CR39","doi-asserted-by":"publisher","first-page":"2829","DOI":"10.1021\/bi101701x","volume":"50","author":"U Golebiewska","year":"2011","unstructured":"Golebiewska, U., Johnston, J. M., Devi, L., Filizola, M. & Scarlata, S. Differential response to morphine of the oligomeric state of \u03bc-opioid in the presence of \u03b4-opioid receptors. Biochemistry 50, 2829\u20132837 (2011)","journal-title":"Biochemistry"},{"key":"BFnature10954_CR40","doi-asserted-by":"publisher","first-page":"1714","DOI":"10.1021\/jm00168a028","volume":"33","author":"PS Portoghese","year":"1990","unstructured":"Portoghese, P. S., Sultana, M. & Takemori, A. E. Design of peptidomimetic \u03b4 opioid receptor antagonists using the message-address concept. J. Med. Chem. 33, 1714\u20131720 (1990)","journal-title":"J. Med. Chem."},{"key":"BFnature10954_CR41","doi-asserted-by":"publisher","first-page":"706","DOI":"10.1038\/nprot.2009.31","volume":"4","author":"M Caffrey","year":"2009","unstructured":"Caffrey, M. & Cherezov, V. Crystallizing membrane proteins using lipidic mesophases. Nature Protocols 4, 706\u2013731 (2009)","journal-title":"Nature Protocols"},{"key":"BFnature10954_CR42","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1016\/S0076-6879(97)76066-X","volume":"276","author":"Z Otwinowski","year":"1997","unstructured":"Otwinowski, Z. & Minor, W. Processing of X-ray diffraction data collected in oscillation mode. Methods Enzymol. 276, 307\u2013326 (1997)","journal-title":"Methods Enzymol."},{"key":"BFnature10954_CR43","doi-asserted-by":"publisher","first-page":"658","DOI":"10.1107\/S0021889807021206","volume":"40","author":"AJ McCoy","year":"2007","unstructured":"McCoy, A. J. et al. Phaser crystallographic software. J. Appl. Cryst. 40, 658\u2013674 (2007)","journal-title":"J. Appl. Cryst."},{"key":"BFnature10954_CR44","doi-asserted-by":"publisher","first-page":"2126","DOI":"10.1107\/S0907444904019158","volume":"60","author":"P Emsley","year":"2004","unstructured":"Emsley, P. & Cowtan, K. Coot: model-building tools for molecular graphics. Acta Crystallogr. D 60, 2126\u20132132 (2004)","journal-title":"Acta Crystallogr. D"},{"key":"BFnature10954_CR45","doi-asserted-by":"publisher","first-page":"850","DOI":"10.1107\/S0907444905007894","volume":"61","author":"PV Afonine","year":"2005","unstructured":"Afonine, P. V., Grosse-Kunstleve, R. W. & Adams, P. D. A robust bulk-solvent correction and anisotropic scaling procedure. Acta Crystallogr. D 61, 850\u2013855 (2005)","journal-title":"Acta Crystallogr. D"},{"key":"BFnature10954_CR46","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1107\/S0907444909042073","volume":"66","author":"VB Chen","year":"2010","unstructured":"Chen, V. B. et al. MolProbity: all-atom structure validation for macromolecular crystallography. Acta Crystallogr. D 66, 12\u201321 (2010)","journal-title":"Acta Crystallogr. D"},{"key":"BFnature10954_CR47","unstructured":"Schrodinger, L. The PyMOL Molecular Graphics System v.1.3r1. (2010)"}],"container-title":["Nature"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/nature10954.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/nature10954","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/nature10954.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T13:59:30Z","timestamp":1684418370000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/nature10954"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,3,21]]},"references-count":47,"journal-issue":{"issue":"7398","published-print":{"date-parts":[[2012,5]]}},"alternative-id":["BFnature10954"],"URL":"https:\/\/doi.org\/10.1038\/nature10954","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.14250956.15764056","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.14250956.15768060","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.14250956.15777119","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.14250956.15768080","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.14250956.15775064","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.14250956.792003067","asserted-by":"object"}]},"ISSN":["0028-0836","1476-4687"],"issn-type":[{"value":"0028-0836","type":"print"},{"value":"1476-4687","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,3,21]]}}}