{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T13:57:17Z","timestamp":1793627837362,"version":"4.5.1"},"reference-count":80,"publisher":"Springer Science and Business Media LLC","issue":"7755","license":[{"start":{"date-parts":[[2019,4,24]],"date-time":"2019-04-24T00:00:00Z","timestamp":1556064000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2019,4,24]],"date-time":"2019-04-24T00:00:00Z","timestamp":1556064000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nature"],"published-print":{"date-parts":[[2019,5,9]]},"DOI":"10.1038\/s41586-019-1141-3","type":"journal-article","created":{"date-parts":[[2019,4,24]],"date-time":"2019-04-24T14:06:46Z","timestamp":1556114806000},"page":"284-288","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":198,"title":["Structural basis of ligand recognition at the human MT1 melatonin receptor"],"prefix":"10.1038","volume":"569","author":[{"given":"Benjamin","family":"Stauch","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda C.","family":"Johansson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John D.","family":"McCorvy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nilkanth","family":"Patel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gye Won","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi-Ping","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cornelius","family":"Gati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Batyuk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel T.","family":"Slocum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrii","family":"Ishchenko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang","family":"Brehm","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas A.","family":"White","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nairie","family":"Michaelian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caleb","family":"Madsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lan","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas D.","family":"Grant","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica M.","family":"Grandner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Shiriaeva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reid H. J.","family":"Olsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra R.","family":"Tribo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sa\u00efd","family":"Yous","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond C.","family":"Stevens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uwe","family":"Weierstall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vsevolod","family":"Katritch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryan L.","family":"Roth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vadim","family":"Cherezov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,4,24]]},"reference":[{"key":"1141_CR1","doi-asserted-by":"publisher","first-page":"1209","DOI":"10.1080\/14728222.2016.1179284","volume":"20","author":"P P\u00e9vet","year":"2016","unstructured":"P\u00e9vet, P. Melatonin receptors as therapeutic targets in the suprachiasmatic nucleus. Expert Opin. Ther. Targets 20, 1209\u20131218 (2016).","journal-title":"Expert Opin. Ther. Targets"},{"key":"1141_CR2","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1016\/j.biocel.2005.08.020","volume":"38","author":"R Hardeland","year":"2006","unstructured":"Hardeland, R., Pandi-Perumal, S. R. & Cardinali, D. P. Melatonin. Int. J. Biochem. Cell Biol. 38, 313\u2013316 (2006).","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"1141_CR3","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1385\/ENDO:27:2:101","volume":"27","author":"ML Dubocovich","year":"2005","unstructured":"Dubocovich, M. L. & Markowska, M. Functional MT1 and MT2 melatonin receptors in mammals. Endocrine 27, 101\u2013110 (2005).","journal-title":"Endocrine"},{"key":"1141_CR4","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1007\/s00441-002-0579-y","volume":"309","author":"S Ganguly","year":"2002","unstructured":"Ganguly, S., Coon, S. L. & Klein, D. C. Control of melatonin synthesis in the mammalian pineal gland: the critical role of serotonin acetylation. Cell Tissue Res. 309, 127\u2013137 (2002).","journal-title":"Cell Tissue Res."},{"key":"1141_CR5","doi-asserted-by":"publisher","first-page":"778","DOI":"10.1002\/bies.201400017","volume":"36","author":"G Tosini","year":"2014","unstructured":"Tosini, G., Owino, S., Guillaume, J. L. & Jockers, R. Understanding melatonin receptor pharmacology: latest insights from mouse models, and their relevance to human disease. BioEssays 36, 778\u2013787 (2014).","journal-title":"BioEssays"},{"key":"1141_CR6","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1124\/pr.110.002832","volume":"62","author":"ML Dubocovich","year":"2010","unstructured":"Dubocovich, M. L. et al. International Union of Basic and Clinical Pharmacology. LXXV. Nomenclature, classification, and pharmacology of G protein-coupled melatonin receptors. Pharmacol. Rev. 62, 343\u2013380 (2010).","journal-title":"Pharmacol. Rev."},{"key":"1141_CR7","first-page":"873","volume":"16","author":"MK Stoller","year":"1994","unstructured":"Stoller, M. K. Economic effects of insomnia. Clin. Ther. 16, 873\u2013897, discussion 854 (1994).","journal-title":"Clin. Ther."},{"key":"1141_CR8","doi-asserted-by":"publisher","first-page":"2702","DOI":"10.1111\/bph.13536","volume":"173","author":"R Jockers","year":"2016","unstructured":"Jockers, R. et al. Update on melatonin receptors: IUPHAR Review 20. Br. J. Pharmacol. 173, 2702\u20132725 (2016).","journal-title":"Br. J. Pharmacol."},{"key":"1141_CR9","doi-asserted-by":"publisher","first-page":"3532","DOI":"10.2174\/092986712801323153","volume":"19","author":"DP Zlotos","year":"2012","unstructured":"Zlotos, D. P. Recent progress in the development of agonists and antagonists for melatonin receptors. Curr. Med. Chem. 19, 3532\u20133549 (2012).","journal-title":"Curr. Med. Chem."},{"key":"1141_CR10","first-page":"1","volume":"79","author":"TC Clarke","year":"2015","unstructured":"Clarke, T. C., Black, L. I., Stussman, B. J., Barnes, P. M. & Nahin, R. L. Trends in the use of complementary health approaches among adults: United States, 2002\u20132012. Natl. Health Stat. Report 79, 1\u201316 (2015).","journal-title":"Natl. Health Stat. Report"},{"key":"1141_CR11","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1358\/dot.2006.42.4.970842","volume":"42","author":"RT Owen","year":"2006","unstructured":"Owen, R. T. Ramelteon: profile of a new sleep-promoting medication. Drugs Today (Barc) 42, 255\u2013263 (2006).","journal-title":"Drugs Today (Barc)"},{"key":"1141_CR12","doi-asserted-by":"publisher","first-page":"954","DOI":"10.1124\/jpet.103.051797","volume":"306","author":"MJ Millan","year":"2003","unstructured":"Millan, M. J. et al. The novel melatonin agonist agomelatine (S20098) is an antagonist at 5-hydroxytryptamine2C receptors, blockade of which enhances the activity of frontocortical dopaminergic and adrenergic pathways. J. Pharmacol. Exp. Ther. 306, 954\u2013964 (2003).","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"1141_CR13","doi-asserted-by":"publisher","first-page":"3604","DOI":"10.1111\/bph.12720","volume":"171","author":"B Guardiola-Lemaitre","year":"2014","unstructured":"Guardiola-Lemaitre, B. et al. Agomelatine: mechanism of action and pharmacological profile in relation to antidepressant properties. Br. J. Pharmacol. 171, 3604\u20133619 (2014).","journal-title":"Br. J. Pharmacol."},{"issue":"7755","key":"1141_CR14","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1038\/s41586-019-1144-0","volume":"569","author":"Linda C. Johansson","year":"2019","unstructured":"Johansson, L. C. et al. XFEL structures of the human MT2 melatonin receptor reveal the basis of subtype selectivity. Nature https:\/\/doi.org\/10.1038\/s41586-019-1144-0 (2019).","journal-title":"Nature"},{"key":"1141_CR15","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1038\/nature14035","volume":"519","author":"J Yin","year":"2015","unstructured":"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\u2013250 (2015).","journal-title":"Nature"},{"key":"1141_CR16","doi-asserted-by":"crossref","unstructured":"Ballesteros, J. A. & Weinstein, H. in Methods in Neurosciences Vol. 25 (ed. Sealfon, S. C.) 366\u2013428 (Academic, 1995).","DOI":"10.1016\/S1043-9471(05)80049-7"},{"key":"1141_CR17","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1016\/j.tibs.2014.03.002","volume":"39","author":"V Katritch","year":"2014","unstructured":"Katritch, V. et al. Allosteric sodium in class A GPCR signaling. Trends Biochem. Sci. 39, 233\u2013244 (2014).","journal-title":"Trends Biochem. Sci."},{"key":"1141_CR18","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1016\/j.str.2017.12.013","volume":"26","author":"KL White","year":"2018","unstructured":"White, K. L. et al. Structural connection between activation microswitch and allosteric sodium site in GPCR signaling. Structure 26, 259\u2013269.e5 (2018).","journal-title":"Structure"},{"key":"1141_CR19","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":"1141_CR20","doi-asserted-by":"publisher","first-page":"1258","DOI":"10.1126\/science.1150577","volume":"318","author":"V Cherezov","year":"2007","unstructured":"Cherezov, V. et al. High-resolution crystal structure of an engineered human \u03b22-adrenergic G protein-coupled receptor. Science 318, 1258\u20131265 (2007).","journal-title":"Science"},{"key":"1141_CR21","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1146\/annurev-biophys-070317-033239","volume":"47","author":"B Stauch","year":"2018","unstructured":"Stauch, B. & Cherezov, V. Serial femtosecond crystallography of G protein-coupled receptors. Annu. Rev. Biophys. 47, 377\u2013397 (2018).","journal-title":"Annu. Rev. Biophys."},{"issue":"D1","key":"1141_CR22","doi-asserted-by":"publisher","first-page":"D356","DOI":"10.1093\/nar\/gkv1178","volume":"44","author":"V Isberg","year":"2016","unstructured":"Isberg, V. et al. GPCRdb: an information system for G protein-coupled receptors. Nucleic Acids Res. 44 (D1), D356\u2013D364 (2016).","journal-title":"Nucleic Acids Res."},{"key":"1141_CR23","doi-asserted-by":"publisher","first-page":"D1083","DOI":"10.1093\/nar\/gkt1031","volume":"42","author":"AP Bento","year":"2014","unstructured":"Bento, A. P. et al. The ChEMBL bioactivity database: an update. Nucleic Acids Res. 42, D1083\u2013D1090 (2014).","journal-title":"Nucleic Acids Res."},{"key":"1141_CR24","first-page":"902","volume":"246","author":"ML Dubocovich","year":"1988","unstructured":"Dubocovich, M. L. Luzindole (N-0774): a novel melatonin receptor antagonist. J. Pharmacol. Exp. Ther. 246, 902\u2013910 (1988).","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"1141_CR25","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1016\/0014-5793(96)00437-1","volume":"386","author":"SM Reppert","year":"1996","unstructured":"Reppert, S. M., Weaver, D. R., Ebisawa, T., Mahle, C. D. & Kolakowski, L. F. Jr Cloning of a melatonin-related receptor from human pituitary. FEBS Lett. 386, 219\u2013224 (1996).","journal-title":"FEBS Lett."},{"key":"1141_CR26","doi-asserted-by":"publisher","first-page":"3281","DOI":"10.1111\/bph.14029","volume":"175","author":"N Clement","year":"2018","unstructured":"Clement, N. et al. Importance of the second extracellular loop for melatonin MT1 receptor function and absence of melatonin binding in GPR50. Br. J. Pharmacol. 175, 3281\u20133297 (2018).","journal-title":"Br. J. Pharmacol."},{"key":"1141_CR27","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/S0074-7742(06)77002-7","volume":"77","author":"EC Azmitia","year":"2007","unstructured":"Azmitia, E. C. Serotonin and brain: evolution, neuroplasticity, and homeostasis. Int. Rev. Neurobiol. 77, 31\u201356 (2007).","journal-title":"Int. Rev. Neurobiol."},{"key":"1141_CR28","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1034\/j.1600-079X.2003.02111.x","volume":"34","author":"DX Tan","year":"2003","unstructured":"Tan, D. X. et al. Melatonin: a hormone, a tissue factor, an autocoid, a paracoid, and an antioxidant vitamin. J. Pineal Res. 34, 75\u201378 (2003).","journal-title":"J. Pineal Res."},{"key":"1141_CR29","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1085\/jgp.201511526","volume":"147","author":"H Yu","year":"2016","unstructured":"Yu, H., Dickson, E. J., Jung, S. R., Koh, D. S. & Hille, B. High membrane permeability for melatonin. J. Gen. Physiol. 147, 63\u201376 (2016).","journal-title":"J. Gen. Physiol."},{"key":"1141_CR30","doi-asserted-by":"publisher","first-page":"4998","DOI":"10.1021\/acs.jmedchem.5b00245","volume":"58","author":"M de la Fuente Revenga","year":"2015","unstructured":"de la Fuente Revenga, M. et al. Novel N-acetyl bioisosteres of melatonin: melatonergic receptor pharmacology, physicochemical studies, and phenotypic assessment of their neurogenic potential. J. Med. Chem. 58, 4998\u20135014 (2015).","journal-title":"J. Med. Chem."},{"key":"1141_CR31","doi-asserted-by":"publisher","first-page":"719","DOI":"10.1016\/j.cell.2018.01.001","volume":"172","author":"Y Peng","year":"2018","unstructured":"Peng, Y. et al. 5-HT2C receptor structures reveal the structural basis of GPCR polypharmacology. Cell 172, 719\u2013730.e14 (2018).","journal-title":"Cell"},{"key":"1141_CR32","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1016\/S0306-4522(99)00011-1","volume":"92","author":"M Pasqualetti","year":"1999","unstructured":"Pasqualetti, M. et al. Distribution and cellular localization of the serotonin type 2C receptor messenger RNA in human brain. Neuroscience 92, 601\u2013611 (1999).","journal-title":"Neuroscience"},{"key":"1141_CR33","doi-asserted-by":"publisher","first-page":"D158","DOI":"10.1093\/nar\/gkw1099","volume":"45","author":"The UniProt Consortium","year":"2017","unstructured":"The UniProt Consortium. UniProt: the universal protein knowledgebase. Nucleic Acids Res. 45, D158\u2013D169 (2017).","journal-title":"Nucleic Acids Res."},{"key":"1141_CR34","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1016\/S0022-2836(05)80360-2","volume":"215","author":"SF Altschul","year":"1990","unstructured":"Altschul, S. F., Gish, W., Miller, W., Myers, E. W. & Lipman, D. J. Basic local alignment search tool. J. Mol. Biol. 215, 403\u2013410 (1990).","journal-title":"J. Mol. Biol."},{"key":"1141_CR35","doi-asserted-by":"publisher","first-page":"W5","DOI":"10.1093\/nar\/gkn201","volume":"36","author":"M Johnson","year":"2008","unstructured":"Johnson, M. et al. NCBI BLAST: a better web interface. Nucleic Acids Res. 36, W5\u2013W9 (2008).","journal-title":"Nucleic Acids Res."},{"key":"1141_CR36","doi-asserted-by":"publisher","first-page":"1073","DOI":"10.1093\/bioinformatics\/btm076","volume":"23","author":"JS Papadopoulos","year":"2007","unstructured":"Papadopoulos, J. S. & Agarwala, R. COBALT: constraint-based alignment tool for multiple protein sequences. Bioinformatics 23, 1073\u20131079 (2007).","journal-title":"Bioinformatics"},{"key":"1141_CR37","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/j.tips.2014.11.001","volume":"36","author":"V Isberg","year":"2015","unstructured":"Isberg, V. et al. Generic GPCR residue numbers \u2014 aligning topology maps while minding the gaps. Trends Pharmacol. Sci. 36, 22\u201331 (2015).","journal-title":"Trends Pharmacol. Sci."},{"key":"1141_CR38","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1214\/aoms\/1177729694","volume":"22","author":"S Kullback","year":"1951","unstructured":"Kullback, S. & Leibler, R. A. On information and sufficiency. Ann. Math. Stat. 22, 79\u201386 (1951).","journal-title":"Ann. Math. Stat."},{"key":"1141_CR39","doi-asserted-by":"publisher","first-page":"508","DOI":"10.1038\/nature11558","volume":"490","author":"JF White","year":"2012","unstructured":"White, J. F. et al. Structure of the agonist-bound neurotensin receptor. Nature 490, 508\u2013513 (2012).","journal-title":"Nature"},{"key":"1141_CR40","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1016\/j.jmb.2009.04.068","volume":"390","author":"Y Shibata","year":"2009","unstructured":"Shibata, Y. et al. Thermostabilization of the neurotensin receptor NTS1. J. Mol. Biol. 390, 262\u2013277 (2009).","journal-title":"J. Mol. Biol."},{"key":"1141_CR41","doi-asserted-by":"publisher","first-page":"1305","DOI":"10.1016\/j.jmb.2007.12.028","volume":"376","author":"CB Roth","year":"2008","unstructured":"Roth, C. B., Hanson, M. A. & Stevens, R. C. Stabilization of the human \u03b22-adrenergic receptor TM4\u2013TM3\u2013TM5 helix interface by mutagenesis of Glu1223.41, a critical residue in GPCR structure. J. Mol. Biol. 376, 1305\u20131319 (2008).","journal-title":"J. Mol. Biol."},{"key":"1141_CR42","doi-asserted-by":"publisher","first-page":"539","DOI":"10.1016\/j.jmb.2008.06.084","volume":"382","author":"S Bhattacharya","year":"2008","unstructured":"Bhattacharya, S., Hall, S. E. & Vaidehi, N. Agonist-induced conformational changes in bovine rhodopsin: insight into activation of G-protein-coupled receptors. J. Mol. Biol. 382, 539\u2013555 (2008).","journal-title":"J. Mol. Biol."},{"key":"1141_CR43","doi-asserted-by":"publisher","first-page":"12010","DOI":"10.1074\/jbc.M600548200","volume":"281","author":"JM Klco","year":"2006","unstructured":"Klco, J. M., Nikiforovich, G. V. & Baranski, T. J. Genetic analysis of the first and third extracellular loops of the C5a receptor reveals an essential WXFG motif in the first loop. J. Biol. Chem. 281, 12010\u201312019 (2006).","journal-title":"J. Biol. Chem."},{"key":"1141_CR44","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. Nat. Protocols 4, 706\u2013731 (2009).","journal-title":"Nat. Protocols"},{"key":"1141_CR45","doi-asserted-by":"publisher","first-page":"2123","DOI":"10.1038\/nprot.2014.141","volume":"9","author":"W Liu","year":"2014","unstructured":"Liu, W., Ishchenko, A. & Cherezov, V. Preparation of microcrystals in lipidic cubic phase for serial femtosecond crystallography. Nat. Protocols 9, 2123\u20132134 (2014).","journal-title":"Nat. Protocols"},{"key":"1141_CR46","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms4309","volume":"5","author":"U Weierstall","year":"2014","unstructured":"Weierstall, U. et al. Lipidic cubic phase injector facilitates membrane protein serial femtosecond crystallography. Nat. Commun. 5, 3309 (2014).","journal-title":"Nat. Commun."},{"key":"1141_CR47","doi-asserted-by":"publisher","first-page":"035024","DOI":"10.1088\/1367-2630\/12\/3\/035024","volume":"12","author":"S Boutet","year":"2010","unstructured":"Boutet, S. & Williams, G. J. The Coherent X-ray Imaging (CXI) instrument at the Linac Coherent Light Source (LCLS). New J. Phys. 12, 035024 (2010).","journal-title":"New J. Phys."},{"key":"1141_CR48","doi-asserted-by":"crossref","unstructured":"Hart, P. et al. The Cornell-SLAC Pixel Array Detector at LCLS. SLAC-PUB https:\/\/ieeexplore.ieee.org\/abstract\/document\/6551166 (2012).","DOI":"10.1109\/NSSMIC.2012.6551166"},{"key":"1141_CR49","doi-asserted-by":"publisher","first-page":"1118","DOI":"10.1107\/S1600576714007626","volume":"47","author":"A Barty","year":"2014","unstructured":"Barty, A. et al. Cheetah: software for high-throughput reduction and analysis of serial femtosecond X-ray diffraction data. J. Appl. Crystallogr. 47, 1118\u20131131 (2014).","journal-title":"J. Appl. Crystallogr."},{"key":"1141_CR50","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1107\/S0021889812002312","volume":"45","author":"TA White","year":"2012","unstructured":"White, T. A. et al. CrystFEL: a software suite for snapshot serial crystallography. J. Appl. Crystallogr. 45, 335\u2013341 (2012).","journal-title":"J. Appl. Crystallogr."},{"key":"1141_CR51","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1107\/S0907444905039107","volume":"62","author":"AG Leslie","year":"2006","unstructured":"Leslie, A. G. The integration of macromolecular diffraction data. Acta Crystallogr. D Biol. Crystallogr. 62, 48\u201357 (2006).","journal-title":"Acta Crystallogr. D Biol. Crystallogr."},{"key":"1141_CR52","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1107\/S0021889891010634","volume":"25","author":"A Duisenberg","year":"1992","unstructured":"Duisenberg, A. Indexing in single-crystal diffractometry with an obstinate list of reflections. J. Appl. Crystallogr. 25, 92\u201396 (1992).","journal-title":"J. Appl. Crystallogr."},{"key":"1141_CR53","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1107\/S0907444909047337","volume":"66","author":"W Kabsch","year":"2010","unstructured":"Kabsch, W. XDS. Acta Crystallogr. D Biol. Crystallogr. 66, 125\u2013132 (2010).","journal-title":"Acta Crystallogr. D Biol. Crystallogr."},{"key":"1141_CR54","doi-asserted-by":"publisher","first-page":"680","DOI":"10.1107\/S1600576716004751","volume":"49","author":"TA White","year":"2016","unstructured":"White, T. A. et al. Recent developments in CrystFEL. J. Appl. Crystallogr. 49, 680\u2013689 (2016).","journal-title":"J. Appl. Crystallogr."},{"key":"1141_CR55","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. Crystallogr. 40, 658\u2013674 (2007).","journal-title":"J. Appl. Crystallogr."},{"key":"1141_CR56","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1107\/S0907444911001314","volume":"67","author":"GN Murshudov","year":"2011","unstructured":"Murshudov, G. N. et al. REFMAC5 for the refinement of macromolecular crystal structures. Acta Crystallogr. D Biol. Crystallogr. 67, 355\u2013367 (2011).","journal-title":"Acta Crystallogr. D Biol. Crystallogr."},{"key":"1141_CR57","unstructured":"BUSTER v. 2.10.2 (Global Phasing Ltd., Cambridge, 2017)."},{"key":"1141_CR58","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1107\/S0907444910007493","volume":"66","author":"P Emsley","year":"2010","unstructured":"Emsley, P., Lohkamp, B., Scott, W. G. & Cowtan, K. Features and development of Coot. Acta Crystallogr. D Biol. Crystallogr. 66, 486\u2013501 (2010).","journal-title":"Acta Crystallogr. D Biol. Crystallogr."},{"key":"1141_CR59","doi-asserted-by":"publisher","first-page":"1355","DOI":"10.1107\/S0907444904011679","volume":"60","author":"AW Sch\u00fcttelkopf","year":"2004","unstructured":"Sch\u00fcttelkopf, A. W. & van Aalten, D. M. PRODRG: a tool for high-throughput crystallography of protein\u2013ligand complexes. Acta Crystallogr. D Biol. Crystallogr. 60, 1355\u20131363 (2004).","journal-title":"Acta Crystallogr. D Biol. Crystallogr."},{"key":"1141_CR60","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 Biol. Crystallogr. 66, 12\u201321 (2010).","journal-title":"Acta Crystallogr. D Biol. Crystallogr."},{"key":"1141_CR61","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1107\/S0907444909052925","volume":"66","author":"PD Adams","year":"2010","unstructured":"Adams, P. D. et al. PHENIX: a comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr. D Biol. Crystallogr. 66, 213\u2013221 (2010).","journal-title":"Acta Crystallogr. D Biol. Crystallogr."},{"key":"1141_CR62","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1016\/j.str.2008.02.004","volume":"16","author":"AI Alexandrov","year":"2008","unstructured":"Alexandrov, A. I., Mileni, M., Chien, E. Y., Hanson, M. A. & Stevens, R. C. Microscale fluorescent thermal stability assay for membrane proteins. Structure 16, 351\u2013359 (2008).","journal-title":"Structure"},{"key":"1141_CR63","doi-asserted-by":"publisher","first-page":"3231","DOI":"10.1021\/jm00046a006","volume":"37","author":"P Depreux","year":"1994","unstructured":"Depreux, P. et al. Synthesis and structure-activity relationships of novel naphthalenic and bioisosteric related amidic derivatives as melatonin receptor ligands. J. Med. Chem. 37, 3231\u20133239 (1994).","journal-title":"J. Med. Chem."},{"key":"1141_CR64","doi-asserted-by":"publisher","first-page":"1484","DOI":"10.1021\/jm00086a018","volume":"35","author":"S Yous","year":"1992","unstructured":"Yous, S. et al. Novel naphthalenic ligands with high affinity for the melatonin receptor. J. Med. Chem. 35, 1484\u20131486 (1992).","journal-title":"J. Med. Chem."},{"key":"1141_CR65","doi-asserted-by":"publisher","first-page":"D370","DOI":"10.1093\/nar\/gkr703","volume":"40","author":"MA Lomize","year":"2012","unstructured":"Lomize, M. A., Pogozheva, I. D., Joo, H., Mosberg, H. I. & Lomize, A. L. OPM database and PPM web server: resources for positioning of proteins in membranes. Nucleic Acids Res. 40, D370\u2013D376 (2012).","journal-title":"Nucleic Acids Res."},{"key":"1141_CR66","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1093\/nar\/28.1.235","volume":"28","author":"HM Berman","year":"2000","unstructured":"Berman, H. M. et al. The Protein Data Bank. Nucleic Acids Res. 28, 235\u2013242 (2000).","journal-title":"Nucleic Acids Res."},{"key":"1141_CR67","doi-asserted-by":"publisher","first-page":"2577","DOI":"10.1002\/bip.360221211","volume":"22","author":"W Kabsch","year":"1983","unstructured":"Kabsch, W. & Sander, C. Dictionary of protein secondary structure: pattern recognition of hydrogen-bonded and geometrical features. Biopolymers 22, 2577\u20132637 (1983).","journal-title":"Biopolymers"},{"key":"1141_CR68","doi-asserted-by":"publisher","first-page":"1422","DOI":"10.1093\/bioinformatics\/btp163","volume":"25","author":"PJ Cock","year":"2009","unstructured":"Cock, P. J. et al. Biopython: freely available Python tools for computational molecular biology and bioinformatics. Bioinformatics 25, 1422\u20131423 (2009).","journal-title":"Bioinformatics"},{"key":"1141_CR69","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1002\/prot.340170108","volume":"17","author":"S Henikoff","year":"1993","unstructured":"Henikoff, S. & Henikoff, J. G. Performance evaluation of amino acid substitution matrices. Proteins 17, 49\u201361 (1993).","journal-title":"Proteins"},{"key":"1141_CR70","doi-asserted-by":"publisher","first-page":"567","DOI":"10.1006\/jmbi.2000.4315","volume":"305","author":"A Krogh","year":"2001","unstructured":"Krogh, A., Larsson, B., von Heijne, G. & Sonnhammer, E. L. Predicting transmembrane protein topology with a hidden Markov model: application to complete genomes. J. Mol. Biol. 305, 567\u2013580 (2001).","journal-title":"J. Mol. Biol."},{"key":"1141_CR71","doi-asserted-by":"publisher","first-page":"921","DOI":"10.1006\/jmbi.1999.3488","volume":"296","author":"A Senes","year":"2000","unstructured":"Senes, A., Gerstein, M. & Engelman, D. M. Statistical analysis of amino acid patterns in transmembrane helices: the GxxxG motif occurs frequently and in association with \u03b2-branched residues at neighboring positions. J. Mol. Biol. 296, 921\u2013936 (2000).","journal-title":"J. Mol. Biol."},{"key":"1141_CR72","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1186\/1758-2946-3-33","volume":"3","author":"NM O\u2019Boyle","year":"2011","unstructured":"O\u2019Boyle, N. M. et al. Open Babel: An open chemical toolbox. J. Cheminform. 3, 33 (2011).","journal-title":"J. Cheminform."},{"key":"1141_CR73","doi-asserted-by":"publisher","first-page":"2684","DOI":"10.1093\/bioinformatics\/btu364","volume":"30","author":"B Kozlikova","year":"2014","unstructured":"Kozlikova, B. et al. CAVER Analyst 1.0: graphic tool for interactive visualization and analysis of tunnels and channels in protein structures. Bioinformatics 30, 2684\u20132685 (2014).","journal-title":"Bioinformatics"},{"key":"1141_CR74","unstructured":"Schr\u00f6dinger, L. L. C. The PyMOL Molecular Graphics System, Version 1.8 (2015)."},{"key":"1141_CR75","doi-asserted-by":"publisher","first-page":"488","DOI":"10.1002\/jcc.540150503","volume":"15","author":"R Abagyan","year":"1994","unstructured":"Abagyan, R., Totrov, M. & Kuznetsov, D. ICM\u2014A new method for protein modeling and design: applications to docking and structure prediction from the distorted native conformation. J. Comput. Chem. 15, 488\u2013506 (1994).","journal-title":"J. Comput. Chem."},{"key":"1141_CR76","doi-asserted-by":"publisher","first-page":"490","DOI":"10.1002\/(SICI)1096-987X(199604)17:5\/6<490::AID-JCC1>3.0.CO;2-P","volume":"17","author":"TA Halgren","year":"1996","unstructured":"Halgren, T. A. Merck molecular force field. I. Basis, form, scope, parameterization, and performance of MMFF94. J. Comput. Chem. 17, 490\u2013519 (1996).","journal-title":"J. Comput. Chem."},{"key":"1141_CR77","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1038\/nature22035","volume":"544","author":"H Zhang","year":"2017","unstructured":"Zhang, H. et al. Structural basis for selectivity and diversity in angiotensin II receptors. Nature 544, 327\u2013332 (2017).","journal-title":"Nature"},{"key":"1141_CR78","doi-asserted-by":"publisher","first-page":"1859","DOI":"10.1002\/jcc.20945","volume":"29","author":"S Jo","year":"2008","unstructured":"Jo, S., Kim, T., Iyer, V. G. & Im, W. CHARMM-GUI: a web-based graphical user interface for CHARMM. J. Comput. Chem. 29, 1859\u20131865 (2008).","journal-title":"J. Comput. Chem."},{"key":"1141_CR79","doi-asserted-by":"publisher","first-page":"1521","DOI":"10.1126\/science.1244142","volume":"342","author":"W Liu","year":"2013","unstructured":"Liu, W. et al. Serial femtosecond crystallography of G protein-coupled receptors. Science 342, 1521\u20131524 (2013).","journal-title":"Science"},{"key":"1141_CR80","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1002\/jcc.21367","volume":"31","author":"K Vanommeslaeghe","year":"2010","unstructured":"Vanommeslaeghe, K. et al. CHARMM general force field: a force field for drug-like molecules compatible with the CHARMM all-atom additive biological force fields. J. Comput. Chem. 31, 671\u2013690 (2010).","journal-title":"J. Comput. Chem."}],"updated-by":[{"DOI":"10.1038\/s41586-019-1209-0","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2019,5,3]],"date-time":"2019-05-03T00:00:00Z","timestamp":1556841600000}}],"container-title":["Nature"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41586-019-1141-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41586-019-1141-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41586-019-1141-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,17]],"date-time":"2024-07-17T03:19:42Z","timestamp":1721186382000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41586-019-1141-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,4,24]]},"references-count":80,"journal-issue":{"issue":"7755","published-print":{"date-parts":[[2019,5,9]]}},"alternative-id":["1141"],"URL":"https:\/\/doi.org\/10.1038\/s41586-019-1141-3","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.735602596.793562812","asserted-by":"object"}]},"ISSN":["0028-0836","1476-4687"],"issn-type":[{"value":"0028-0836","type":"print"},{"value":"1476-4687","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,4,24]]},"assertion":[{"value":"28 July 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 March 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 April 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 May 2019","order":4,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Correction","order":5,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"<b>Change history:<\/b> In this Letter, the rotation signs around 90\u00b0, 135\u00b0 and 15\u00b0 were missing\u00a0and in the HTML, Extended Data Tables 2 and 3 were the wrong tables; these errors have been corrected online.","order":6,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}