{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T20:06:18Z","timestamp":1792613178748,"version":"4.5.0"},"reference-count":64,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2025,1,20]],"date-time":"2025-01-20T00:00:00Z","timestamp":1737331200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2025,1,20]],"date-time":"2025-01-20T00:00:00Z","timestamp":1737331200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Struct Mol Biol"],"published-print":{"date-parts":[[2025,3]]},"DOI":"10.1038\/s41594-024-01481-6","type":"journal-article","created":{"date-parts":[[2025,1,20]],"date-time":"2025-01-20T10:05:12Z","timestamp":1737367512000},"page":"531-542","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["The structure and function of the ghrelin receptor coding for drug actions"],"prefix":"10.1038","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9752-7399","authenticated-orcid":false,"given":"Yuki","family":"Shiimura","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6939-7718","authenticated-orcid":false,"given":"Dohyun","family":"Im","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryosuke","family":"Tany","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hidetsugu","family":"Asada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryoji","family":"Kise","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eon","family":"Kurumiya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideko","family":"Wakasugi-Masuho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3555-1083","authenticated-orcid":false,"given":"Satoshi","family":"Yasuda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-0113-8449","authenticated-orcid":false,"given":"Kazuma","family":"Matsui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3913-7330","authenticated-orcid":false,"given":"Jun-ichi","family":"Kishikawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8879-6685","authenticated-orcid":false,"given":"Takayuki","family":"Kato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5748-4670","authenticated-orcid":false,"given":"Takeshi","family":"Murata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3153-0341","authenticated-orcid":false,"given":"Masayasu","family":"Kojima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1735-2937","authenticated-orcid":false,"given":"So","family":"Iwata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8754-987X","authenticated-orcid":false,"given":"Ikuo","family":"Masuho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,1,20]]},"reference":[{"key":"1481_CR1","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1038\/45230","volume":"402","author":"M Kojima","year":"1999","unstructured":"Kojima, M. et al. Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 402, 656\u2013660 (1999).","journal-title":"Nature"},{"key":"1481_CR2","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1126\/science.273.5277.974","volume":"273","author":"AD Howard","year":"1996","unstructured":"Howard, A. D. et al. A receptor in pituitary and hypothalamus that functions in growth hormone release. Science 273, 974\u2013977 (1996).","journal-title":"Science"},{"key":"1481_CR3","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1038\/35051587","volume":"409","author":"M Nakazato","year":"2001","unstructured":"Nakazato, M. et al. A role for ghrelin in the central regulation of feeding. Nature 409, 194\u2013198 (2001).","journal-title":"Nature"},{"key":"1481_CR4","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1006\/bbrc.2000.3568","volume":"276","author":"Y Masuda","year":"2000","unstructured":"Masuda, Y. et al. Ghrelin stimulates gastric acid secretion and motility in rats. Biochem. Biophys. Res. Commun. 276, 905\u2013908 (2000).","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"1481_CR5","doi-asserted-by":"crossref","first-page":"14069","DOI":"10.1073\/pnas.0903090106","volume":"106","author":"E Szentirmai","year":"2009","unstructured":"Szentirmai, E., Kapas, L., Sun, Y., Smith, R. G. & Krueger, J. M. The preproghrelin gene is required for the normal integration of thermoregulation and sleep in mice. Proc. Natl Acad. Sci. USA 106, 14069\u201314074 (2009).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1481_CR6","doi-asserted-by":"crossref","first-page":"798","DOI":"10.3390\/ijms18040798","volume":"18","author":"G Collden","year":"2017","unstructured":"Collden, G., Tschop, M. H. & Muller, T. D. Therapeutic potential of targeting the ghrelin pathway. Int. J. Mol. Sci. 18, 798 (2017).","journal-title":"Int. J. Mol. Sci."},{"key":"1481_CR7","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1172\/JCI25303","volume":"116","author":"J Pantel","year":"2006","unstructured":"Pantel, J. et al. Loss of constitutive activity of the growth hormone secretagogue receptor in familial short stature. J. Clin. Invest. 116, 760\u2013768 (2006).","journal-title":"J. Clin. Invest."},{"key":"1481_CR8","doi-asserted-by":"crossref","first-page":"E373","DOI":"10.1210\/jc.2010-1570","volume":"96","author":"H Inoue","year":"2011","unstructured":"Inoue, H. et al. Identification and functional analysis of novel human growth hormone secretagogue receptor (GHSR) gene mutations in Japanese subjects with short stature. J. Clin. Endocrinol. Metab. 96, E373\u2013E378 (2011).","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"1481_CR9","doi-asserted-by":"crossref","first-page":"4334","DOI":"10.1210\/jc.2009-1327","volume":"94","author":"J Pantel","year":"2009","unstructured":"Pantel, J. et al. Recessive isolated growth hormone deficiency and mutations in the ghrelin receptor. J. Clin. Endocrinol. Metab. 94, 4334\u20134341 (2009).","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"1481_CR10","doi-asserted-by":"crossref","first-page":"1256","DOI":"10.1124\/mol.63.6.1256","volume":"63","author":"R Fredriksson","year":"2003","unstructured":"Fredriksson, R., Lagerstrom, M. C., Lundin, L. G. & Schioth, H. B. The G-protein-coupled receptors in the human genome form five main families. Phylogenetic analysis, paralogon groups, and fingerprints. Mol. Pharmacol. 63, 1256\u20131272 (2003).","journal-title":"Mol. Pharmacol."},{"key":"1481_CR11","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/S0079-6107(03)00052-X","volume":"83","author":"S Offermanns","year":"2003","unstructured":"Offermanns, S. G-proteins as transducers in transmembrane signalling. Prog. Biophys. Mol. Biol. 83, 101\u2013130 (2003).","journal-title":"Prog. Biophys. Mol. Biol."},{"key":"1481_CR12","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1006\/geno.1999.5992","volume":"62","author":"GB Downes","year":"1999","unstructured":"Downes, G. B. & Gautam, N. The G protein subunit gene families. Genomics 62, 544\u2013552 (1999).","journal-title":"Genomics"},{"key":"1481_CR13","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1152\/physrev.00003.2005","volume":"85","author":"N Wettschureck","year":"2005","unstructured":"Wettschureck, N. & Offermanns, S. Mammalian G proteins and their cell type specific functions. Physiol. Rev. 85, 1159\u20131204 (2005).","journal-title":"Physiol. Rev."},{"key":"1481_CR14","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1038\/nrd.2017.178","volume":"16","author":"AS Hauser","year":"2017","unstructured":"Hauser, A. S., Attwood, M. M., Rask-Andersen, M., Schioth, H. B. & Gloriam, D. E. Trends in GPCR drug discovery: new agents, targets and indications. Nat. Rev. Drug Discov. 16, 829\u2013842 (2017).","journal-title":"Nat. Rev. Drug Discov."},{"key":"1481_CR15","doi-asserted-by":"crossref","first-page":"17m11585","DOI":"10.4088\/JCP.17m11585","volume":"79","author":"PK Fazeli","year":"2018","unstructured":"Fazeli, P. K. et al. Treatment with a ghrelin agonist in outpatient women with anorexia nervosa: a randomized clinical trial. J. Clin. Psychiatry 79, 17m11585 (2018).","journal-title":"J. Clin. Psychiatry"},{"key":"1481_CR16","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1038\/ncpendmet0625","volume":"3","author":"P Wiedmer","year":"2007","unstructured":"Wiedmer, P., Nogueiras, R., Broglio, F., D\u2019Alessio, D. & Tschop, M. H. Ghrelin, obesity and diabetes. Nat. Clin. Pract. Endocrinol. Metab. 3, 705\u2013712 (2007).","journal-title":"Nat. Clin. Pract. Endocrinol. Metab."},{"key":"1481_CR17","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/S1470-2045(15)00558-6","volume":"17","author":"JS Temel","year":"2016","unstructured":"Temel, J. S. et al. Anamorelin in patients with non-small-cell lung cancer and cachexia (ROMANA 1 and ROMANA 2): results from two randomised, double-blind, phase 3 trials. Lancet Oncol. 17, 519\u2013531 (2016).","journal-title":"Lancet Oncol."},{"key":"1481_CR18","volume":"12","author":"Y Wang","year":"2021","unstructured":"Wang, Y. et al. Molecular recognition of an acyl-peptide hormone and activation of ghrelin receptor. Nat. Commun. 12, 5064 (2021).","journal-title":"Nat. Commun."},{"key":"1481_CR19","volume":"13","author":"J Qin","year":"2022","unstructured":"Qin, J. et al. Molecular mechanism of agonism and inverse agonism in ghrelin receptor. Nat. Commun. 13, 300 (2022).","journal-title":"Nat. Commun."},{"key":"1481_CR20","volume":"12","author":"H Liu","year":"2021","unstructured":"Liu, H. et al. Structural basis of human ghrelin receptor signaling by ghrelin and the synthetic agonist ibutamoren. Nat. Commun. 12, 6410 (2021).","journal-title":"Nat. Commun."},{"key":"1481_CR21","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-020-17554-1","volume":"11","author":"Y Shiimura","year":"2020","unstructured":"Shiimura, Y. et al. Structure of an antagonist-bound ghrelin receptor reveals possible ghrelin recognition mode. Nat. Commun. 11, 4160 (2020).","journal-title":"Nat. Commun."},{"key":"1481_CR22","doi-asserted-by":"crossref","first-page":"ra123","DOI":"10.1126\/scisignal.aab4068","volume":"8","author":"I Masuho","year":"2015","unstructured":"Masuho, I. et al. Distinct profiles of functional discrimination among G proteins determine the actions of G protein-coupled receptors. Sci. Signal. 8, ra123 (2015).","journal-title":"Sci. Signal."},{"key":"1481_CR23","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1111\/bcpt.13228","volume":"126","author":"I Masuho","year":"2020","unstructured":"Masuho, I., Skamangas, N. K. & Martemyanov, K. A. Live cell optical assay for precise characterization of receptors coupling to G\u03b112. Basic Clin. Pharmacol. Toxicol. 126, 88\u201395 (2020).","journal-title":"Basic Clin. Pharmacol. Toxicol."},{"key":"1481_CR24","doi-asserted-by":"crossref","first-page":"25129","DOI":"10.1074\/jbc.M113.462283","volume":"288","author":"I Masuho","year":"2013","unstructured":"Masuho, I., Xie, K. & Martemyanov, K. A. Macromolecular composition dictates receptor and G protein selectivity of regulator of G protein signaling (RGS) 7 and 9\u20142 protein complexes in living cells. J. Biol. Chem. 288, 25129\u201325142 (2013).","journal-title":"J. Biol. Chem."},{"key":"1481_CR25","doi-asserted-by":"crossref","first-page":"15175","DOI":"10.1074\/jbc.270.25.15175","volume":"270","author":"S Offermanns","year":"1995","unstructured":"Offermanns, S. & Simon, M. I. G\u03b115 and G\u03b116 couple a wide variety of receptors to phospholipase C. J. Biol. Chem. 270, 15175\u201315180 (1995).","journal-title":"J. Biol. Chem."},{"key":"1481_CR26","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1016\/j.cell.2020.08.052","volume":"183","author":"I Masuho","year":"2020","unstructured":"Masuho, I. et al. A global map of G protein signaling regulation by RGS proteins. Cell 183, 503\u2013521 (2020).","journal-title":"Cell"},{"key":"1481_CR27","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1126\/science.aaw5188","volume":"364","author":"S Maeda","year":"2019","unstructured":"Maeda, S., Qu, Q., Robertson, M. J., Skiniotis, G. & Kobilka, B. K. Structures of the M1 and M2 muscarinic acetylcholine receptor\/G-protein complexes. Science 364, 552\u2013557 (2019).","journal-title":"Science"},{"key":"1481_CR28","doi-asserted-by":"crossref","first-page":"15799","DOI":"10.1074\/jbc.M609796200","volume":"282","author":"B Holst","year":"2007","unstructured":"Holst, B. et al. Identification of an efficacy switch region in the ghrelin receptor responsible for interchange between agonism and inverse agonism. J. Biol. Chem. 282, 15799\u201315811 (2007).","journal-title":"J. Biol. Chem."},{"key":"1481_CR29","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1038\/nrd705","volume":"1","author":"DM Roden","year":"2002","unstructured":"Roden, D. M. & George, A. L.Jr The genetic basis of variability in drug responses. Nat. Rev. Drug Discov. 1, 37\u201344 (2002).","journal-title":"Nat. Rev. Drug Discov."},{"key":"1481_CR30","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1038\/nrg.2016.49","volume":"17","author":"S Goodwin","year":"2016","unstructured":"Goodwin, S., McPherson, J. D. & McCombie, W. R. Coming of age: ten years of next-generation sequencing technologies. Nat. Rev. Genet. 17, 333\u2013351 (2016).","journal-title":"Nat. Rev. Genet."},{"key":"1481_CR31","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1038\/jhg.2013.114","volume":"59","author":"B Rabbani","year":"2014","unstructured":"Rabbani, B., Tekin, M. & Mahdieh, N. The promise of whole-exome sequencing in medical genetics. J. Hum. Genet. 59, 5\u201315 (2014).","journal-title":"J. Hum. Genet."},{"key":"1481_CR32","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1038\/s41586-020-2308-7","volume":"581","author":"KJ Karczewski","year":"2020","unstructured":"Karczewski, K. J. et al. The mutational constraint spectrum quantified from variation in 141,456 humans. Nature 581, 434\u2013443 (2020).","journal-title":"Nature"},{"key":"1481_CR33","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1086\/513473","volume":"80","author":"GV Kryukov","year":"2007","unstructured":"Kryukov, G. V., Pennacchio, L. A. & Sunyaev, S. R. Most rare missense alleles are deleterious in humans: implications for complex disease and association studies. Am. J. Hum. Genet. 80, 727\u2013739 (2007).","journal-title":"Am. J. Hum. Genet."},{"key":"1481_CR34","doi-asserted-by":"crossref","first-page":"1320","DOI":"10.1038\/ejhg.2012.68","volume":"20","author":"S Subramanian","year":"2012","unstructured":"Subramanian, S. Quantifying harmful mutations in human populations. Eur. J. Hum. Genet. 20, 1320\u20131322 (2012).","journal-title":"Eur. J. Hum. Genet."},{"key":"1481_CR35","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1038\/nrg.2016.86","volume":"17","author":"EA Ashley","year":"2016","unstructured":"Ashley, E. A. Towards precision medicine. Nat. Rev. Genet. 17, 507\u2013522 (2016).","journal-title":"Nat. Rev. Genet."},{"key":"1481_CR36","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.cell.2017.11.033","volume":"172","author":"AS Hauser","year":"2018","unstructured":"Hauser, A. S. et al. Pharmacogenomics of GPCR drug targets. Cell 172, 41\u201354 (2018).","journal-title":"Cell"},{"key":"1481_CR37","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.cell.2020.03.003","volume":"181","author":"M Congreve","year":"2020","unstructured":"Congreve, M., de Graaf, C., Swain, N. A. & Tate, C. G. Impact of GPCR structures on drug discovery. Cell 181, 81\u201391 (2020).","journal-title":"Cell"},{"key":"1481_CR38","doi-asserted-by":"crossref","first-page":"D335","DOI":"10.1093\/nar\/gkaa1080","volume":"49","author":"AJ Kooistra","year":"2021","unstructured":"Kooistra, A. J. et al. GPCRdb in 2021: integrating GPCR sequence, structure and function. Nucleic Acids Res. 49, D335\u2013D343 (2021).","journal-title":"Nucleic Acids Res."},{"key":"1481_CR39","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1126\/science.aan5468","volume":"358","author":"S Wang","year":"2017","unstructured":"Wang, S. et al. D4 dopamine receptor high-resolution structures enable the discovery of selective agonists. Science 358, 381\u2013386 (2017).","journal-title":"Science"},{"key":"1481_CR40","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1038\/s41586-020-2027-0","volume":"579","author":"RM Stein","year":"2020","unstructured":"Stein, R. M. et al. Virtual discovery of melatonin receptor ligands to modulate circadian rhythms. Nature 579, 609\u2013614 (2020).","journal-title":"Nature"},{"key":"1481_CR41","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1038\/s41586-019-0917-9","volume":"566","author":"J Lyu","year":"2019","unstructured":"Lyu, J. et al. Ultra-large library docking for discovering new chemotypes. Nature 566, 224\u2013229 (2019).","journal-title":"Nature"},{"key":"1481_CR42","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/S0163-7258(03)00051-2","volume":"99","author":"E Hermans","year":"2003","unstructured":"Hermans, E. Biochemical and pharmacological control of the multiplicity of coupling at G-protein-coupled receptors. Pharmacol. Ther. 99, 25\u201344 (2003).","journal-title":"Pharmacol. Ther."},{"key":"1481_CR43","doi-asserted-by":"crossref","first-page":"1933","DOI":"10.1016\/j.cell.2019.04.044","volume":"177","author":"A Inoue","year":"2019","unstructured":"Inoue, A. et al. Illuminating G-protein-coupling selectivity of GPCRs. Cell 177, 1933\u20131947 (2019).","journal-title":"Cell"},{"key":"1481_CR44","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.74101","volume":"11","author":"C Avet","year":"2022","unstructured":"Avet, C. et al. Effector membrane translocation biosensors reveal G protein and \u03b2arrestin coupling profiles of 100 therapeutically relevant GPCRs. eLife 11, e74101 (2022).","journal-title":"eLife"},{"key":"1481_CR45","doi-asserted-by":"crossref","first-page":"2074","DOI":"10.1016\/j.celrep.2017.10.108","volume":"21","author":"S Himmelreich","year":"2017","unstructured":"Himmelreich, S. et al. Dopamine receptor DAMB signals via Gq to mediate forgetting in Drosophila. Cell Rep. 21, 2074\u20132081 (2017).","journal-title":"Cell Rep."},{"key":"1481_CR46","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1093\/gbe\/evu038","volume":"6","author":"A de Mendoza","year":"2014","unstructured":"de Mendoza, A., Sebe-Pedros, A. & Ruiz-Trillo, I. The evolution of the GPCR signaling system in eukaryotes: modularity, conservation, and the transition to metazoan multicellularity. Genome Biol. Evol. 6, 606\u2013619 (2014).","journal-title":"Genome Biol. Evol."},{"key":"1481_CR47","doi-asserted-by":"crossref","first-page":"E10255","DOI":"10.1073\/pnas.1804003115","volume":"115","author":"F Mende","year":"2018","unstructured":"Mende, F. et al. Translating biased signaling in the ghrelin receptor system into differential in vivo functions. Proc. Natl Acad. Sci. USA 115, E10255\u2013E10264 (2018).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1481_CR48","doi-asserted-by":"crossref","first-page":"2319","DOI":"10.2337\/db07-0345","volume":"56","author":"K Dezaki","year":"2007","unstructured":"Dezaki, K., Kakei, M. & Yada, T. Ghrelin uses G\u03b1i2 and activates voltage-dependent K+ channels to attenuate glucose-induced Ca2+ signaling and insulin release in islet \u03b2-cells: novel signal transduction of ghrelin. Diabetes 56, 2319\u20132327 (2007).","journal-title":"Diabetes"},{"key":"1481_CR49","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1124\/pharmrev.120.000011","volume":"73","author":"T Schoneberg","year":"2021","unstructured":"Schoneberg, T. & Liebscher, I. Mutations in G protein-coupled receptors: mechanisms, pathophysiology and potential therapeutic approaches. Pharmacol. Rev. 73, 89\u2013119 (2021).","journal-title":"Pharmacol. Rev."},{"key":"1481_CR50","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1038\/nature09410","volume":"467","author":"H Lango Allen","year":"2010","unstructured":"Lango Allen, H. et al. Hundreds of variants clustered in genomic loci and biological pathways affect human height. Nature 467, 832\u2013838 (2010).","journal-title":"Nature"},{"key":"1481_CR51","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1016\/j.cellsig.2009.02.017","volume":"21","author":"B Hollins","year":"2009","unstructured":"Hollins, B., Kuravi, S., Digby, G. J. & Lambert, N. A. The C-terminus of GRK3 indicates rapid dissociation of G protein heterotrimers. Cell Signal. 21, 1015\u20131021 (2009).","journal-title":"Cell Signal."},{"key":"1481_CR52","doi-asserted-by":"crossref","first-page":"11","DOI":"10.3389\/neuro.03.011.2009","volume":"3","author":"C Fenech","year":"2009","unstructured":"Fenech, C. et al. Ric-8A, a G\u03b1 protein guanine nucleotide exchange factor potentiates taste receptor signaling. Front. Cell. Neurosci. 3, 11 (2009).","journal-title":"Front. Cell. Neurosci."},{"key":"1481_CR53","doi-asserted-by":"crossref","first-page":"9310","DOI":"10.1073\/pnas.0600697103","volume":"103","author":"LE Von Dannecker","year":"2006","unstructured":"Von Dannecker, L. E., Mercadante, A. F. & Malnic, B. Ric-8B promotes functional expression of odorant receptors. Proc. Natl Acad. Sci. USA 103, 9310\u20139314 (2006).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1481_CR54","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1016\/j.cell.2010.10.018","volume":"143","author":"A Raveh","year":"2010","unstructured":"Raveh, A., Cooper, A., Guy-David, L. & Reuveny, E. Nonenzymatic rapid control of GIRK channel function by a G protein-coupled receptor kinase. Cell 143, 750\u2013760 (2010).","journal-title":"Cell"},{"key":"1481_CR55","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1038\/nmeth.4193","volume":"14","author":"SQ Zheng","year":"2017","unstructured":"Zheng, S. Q. et al. MotionCor2: anisotropic correction of beam-induced motion for improved cryo-electron microscopy. Nat. Methods 14, 331\u2013332 (2017).","journal-title":"Nat. Methods"},{"key":"1481_CR56","first-page":"4652685","volume":"2017","author":"FP Ferreira","year":"2017","unstructured":"Ferreira, F. P., Goulart, M. D., de Almeida-Pedrin, R. R., Conti, A. C. & Cardoso, M. A. Treatment of class III malocclusion: atypical extraction protocol. Case Rep. Dent. 2017, 4652685 (2017).","journal-title":"Case Rep. Dent."},{"key":"1481_CR57","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-020-18952-1","volume":"11","author":"T Bepler","year":"2020","unstructured":"Bepler, T., Kelley, K., Noble, A. J. & Berger, B. Topaz-Denoise: general deep denoising models for cryoEM and cryoET. Nat. Commun. 11, 5208 (2020).","journal-title":"Nat. Commun."},{"key":"1481_CR58","doi-asserted-by":"crossref","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":"1481_CR59","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1107\/S2059798318006551","volume":"74","author":"PV Afonine","year":"2018","unstructured":"Afonine, P. V. et al. Real-space refinement in PHENIX for cryo-EM and crystallography. Acta Crystallogr. D Struct. Biol. 74, 531\u2013544 (2018).","journal-title":"Acta Crystallogr. D Struct. Biol."},{"key":"1481_CR60","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1002\/pro.3235","volume":"27","author":"TD Goddard","year":"2018","unstructured":"Goddard, T. D. et al. UCSF ChimeraX: meeting modern challenges in visualization and analysis. Protein Sci. 27, 14\u201325 (2018).","journal-title":"Protein Sci."},{"key":"1481_CR61","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1007\/978-1-4939-2914-6_8","volume":"1335","author":"I Masuho","year":"2015","unstructured":"Masuho, I., Martemyanov, K. A. & Lambert, N. A. Monitoring G protein activation in cells with BRET. Methods Mol. Biol. 1335, 107\u2013113 (2015).","journal-title":"Methods Mol. Biol."},{"key":"1481_CR62","doi-asserted-by":"crossref","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":"1481_CR63","doi-asserted-by":"crossref","first-page":"1997","DOI":"10.1002\/jcc.23702","volume":"35","author":"EL Wu","year":"2014","unstructured":"Wu, E. L. et al. CHARMM-GUI Membrane Builder toward realistic biological membrane simulations. J. Comput. Chem. 35, 1997\u20132004 (2014).","journal-title":"J. Comput. Chem."},{"key":"1481_CR64","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."}],"container-title":["Nature Structural &amp; Molecular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41594-024-01481-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41594-024-01481-6","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41594-024-01481-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,18]],"date-time":"2025-03-18T15:08:42Z","timestamp":1742310522000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41594-024-01481-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,20]]},"references-count":64,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,3]]}},"alternative-id":["1481"],"URL":"https:\/\/doi.org\/10.1038\/s41594-024-01481-6","relation":{},"ISSN":["1545-9993","1545-9985"],"issn-type":[{"value":"1545-9993","type":"print"},{"value":"1545-9985","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,20]]},"assertion":[{"value":"30 October 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 December 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 January 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}