Structural basis of ligand recognition and activation of the histamine receptor family.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
27 Sep 2024
27 Sep 2024
Historique:
received:
06
01
2024
accepted:
12
09
2024
medline:
28
9
2024
pubmed:
28
9
2024
entrez:
27
9
2024
Statut:
epublish
Résumé
Histamine is a biogenic amine that is critical in various physiological and pathophysiological processes, including but not limited to allergic reactions, wakefulness, gastric acid secretion and neurotransmission. Here, we determine 9 cryo-electron microscopy (cryo-EM) structures of the 4 histamine receptors in complex with four different G protein subtypes, with endogenous or synthetic agonists bound. Inside the ligand pocket, we identify key motifs for the recognition of histamine, the distinct binding orientations of histamine and three subpockets that facilitate the design of specific ligands. In addition, we also identify key residues responsible for the selectivity of immethridine. Moreover, we reveal distinct structural features as determinants of Gq vs. Gs or Gs vs. Gi coupling differences among the histamine receptors. Our study provides a structural framework for understanding the ligand recognition and G protein coupling of all 4 histamine receptors, which may facilitate the rational design of ligands targeting these receptors.
Identifiants
pubmed: 39333117
doi: 10.1038/s41467-024-52585-y
pii: 10.1038/s41467-024-52585-y
doi:
Substances chimiques
Ligands
0
Histamine
820484N8I3
Receptors, Histamine
0
Histamine Agonists
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
8296Subventions
Organisme : Ministry of Science and Technology of the People's Republic of China (Chinese Ministry of Science and Technology)
ID : 2019YFA0904100
Informations de copyright
© 2024. The Author(s).
Références
Haas, H. L., Sergeeva, O. A. & Selbach, O. Histamine in the nervous system. Physiol. Rev. 88, 1183–1241 (2008).
pubmed: 18626069
doi: 10.1152/physrev.00043.2007
Garbarg, M., Barbin, G., Feger, J. & Schwartz, J. C. Histaminergic pathway in rat-brain evidenced by lesions of medial forebrain-bundle. Science 186, 833–835 (1974).
pubmed: 4157144
doi: 10.1126/science.186.4166.833
Akdis, C. A. & Blaser, K. Histamine in the immune regulation of allergic inflammation. J. Allergy Clin. Immunol. 112, 15–22 (2003).
pubmed: 12847474
doi: 10.1067/mai.2003.1585
Metcalfe, D. D., Baram, D. & Mekori, Y. A. Mast cells. Physiol. Rev. 77, 1033–1079 (1997).
pubmed: 9354811
doi: 10.1152/physrev.1997.77.4.1033
Wernersson, S. & Pejler, G. Mast cell secretory granules: armed for battle. Nat. Rev. Immunol. 14, 478–494 (2014).
pubmed: 24903914
doi: 10.1038/nri3690
Fulkerson, P. C. & Rothenberg, M. E. Targeting eosinophils in allergy, inflammation and beyond. Nat. Rev. Drug Discov. 12, 117–129 (2013).
pubmed: 23334207
doi: 10.1038/nrd3838
Gantz, I. et al. Molecular-cloning of a gene encoding the histamine-H2-receptor. Proc. Natl Acad. Sci. USA 88, 429–433 (1991).
pubmed: 1703298
pmcid: 50824
doi: 10.1073/pnas.88.2.429
Morisset, S. et al. High constitutive activity of native H(3) receptors regulates histamine neurons in brain. Nature 408, 860–864 (2000).
pubmed: 11130725
doi: 10.1038/35048583
Yokoyama, H. The role of central histaminergic neuron system as an anticonvulsive mechanism in developing brain. Brain Dev. 23, 542–547 (2001).
pubmed: 11701252
doi: 10.1016/S0387-7604(01)00261-3
Parsons, M. E. & Ganellin, C. R. Histamine and its receptors. Br. J. Pharmacol. 147, S127–S135 (2006).
pubmed: 16402096
pmcid: 1760721
doi: 10.1038/sj.bjp.0706440
Leconiat, M., Traiffort, E., Ruat, M., Arrang, J. M. & Berger, R. Chromosomal localization of the human histamine H-1-receptor gene. Hum. Genet. 94, 186–188 (1994).
doi: 10.1007/BF00202867
Oda, T., Morikawa, N., Saito, Y., Masuho, Y. & Matsumoto, S. Molecular cloning and characterization of a novel type of histamine receptor preferentially expressed in leukocytes. J. Biol. Chem. 275, 36781–36786 (2000).
pubmed: 10973974
doi: 10.1074/jbc.M006480200
Lovenberg, T. W. et al. Cloning and functional expression of the human histamine H-3 receptor. Mol. Pharmacol. 55, 1101–1107 (1999).
pubmed: 10347254
doi: 10.1124/mol.55.6.1101
Thurmond, R. L., Gelfand, E. W. & Dunford, P. J. The role of histamine H-1 and H-4 receptors in allergic inflammation: the search for new antihistamines. Nat. Rev. Drug Discov. 7, 41–53 (2008).
pubmed: 18172439
doi: 10.1038/nrd2465
Panula, P. et al. International union of basic and clinical pharmacology. XCVIII. Histamine receptors. Pharmacol. Rev. 67, 601–655 (2015).
pubmed: 26084539
pmcid: 4485016
doi: 10.1124/pr.114.010249
Leurs, R., Smit, M. J. & Timmerman, H. Molecular pharmacological aspects of histamine-receptors. Pharmacol. Therap. 66, 413–463 (1995).
doi: 10.1016/0163-7258(95)00006-3
Dauvilliers, Y. et al. Pitolisant versus placebo or modafinil in patients with narcolepsy: a double-blind, randomised trial. Lancet Neurol. 12, 1068–1075 (2013).
pubmed: 24107292
doi: 10.1016/S1474-4422(13)70225-4
Simons, F. E. R. Drug therapy - advances in H-1-antihistamines. N. Engl. J. Med. 351, 2203–2217 (2004).
pubmed: 15548781
doi: 10.1056/NEJMra033121
Simons, F. E. R. & Simons, K. J. Histamine and H-1-antihistamines: celebrating a century of progress. J. Allergy Clin. Immunol. 128, 1139 (2011).
pubmed: 22035879
doi: 10.1016/j.jaci.2011.09.005
Hershcovici, T. & Fass, R. Gastro-oesophageal reflux disease beyond proton pump inhibitor therapy. Drugs 71, 2381–2389 (2011).
pubmed: 22117130
doi: 10.2165/11597300-000000000-00000
Sigterman, K. E., van Pinxteren, B., Bonis, P. A., Lau, J. & Numans, M. E. Short-term treatment with proton pump inhibitors, H2-receptor antagonists and prokinetics for gastro-oesophageal reflux disease-like symptoms and endoscopy negative reflux disease. Cochrane Database Syst. Rev. 2013, CD002095 (2013).
pubmed: 23728637
pmcid: 7066537
Nguyen, P. L. & Cho, J. Pathophysiological roles of histamine receptors in cancer progression: implications and perspectives as potential molecular targets. Biomolecules 11, 1232 (2021).
pubmed: 34439898
pmcid: 8392479
doi: 10.3390/biom11081232
Kimura, S. et al. Relationship between CCL22 expression by vascular smooth muscle cells and macrophage histamine receptors in atherosclerosis. J. Atheroscler. Thromb. 25, 1240–1254 (2018).
pubmed: 29794410
pmcid: 6249366
doi: 10.5551/jat.44297
Cao, J. et al. H(1)R mediates local anesthetic-induced vascular permeability in angioedema. Toxicol. Appl. Pharm. 392, 114921 (2020).
doi: 10.1016/j.taap.2020.114921
Kawakami, N., Miyoshi, K., Horio, S. & Fukui, H. Beta(2)-adrenergic receptor-mediated histamine H(1) receptor down-regulation: another possible advantage of beta(2) agonists in asthmatic therapy. J. Pharm. Sci. 94, 449–458 (2004).
doi: 10.1254/jphs.94.449
Masini, E., Blandina, P., Brunelleschi, S. & Mannaioni, P. F. Evidence for H2-receptor-mediated inhibition of histamine release from isolated rat mast cells. Agents Actions 12, 85–88 (1982).
pubmed: 6177221
doi: 10.1007/BF01965111
Clark, R. A., Gallin, J. I. & Kaplan, A. P. The selective eosinophil chemotactic activity of histamine. J. Exp. Med. 142, 1462–1476 (1975).
pubmed: 450
doi: 10.1084/jem.142.6.1462
Frei, R. et al. Histamine receptor 2 modifies dendritic cell responses to microbial ligands. J. Allergy Clin. Immunol. 132, 194–204 (2013).
pubmed: 23465664
doi: 10.1016/j.jaci.2013.01.013
Mazzoni, A. et al. Cutting edge: histamine inhibits IFN-alpha release from plasmacytoid dendritic cells. J. Immunol. 170, 2269–2273 (2003).
pubmed: 12594246
doi: 10.4049/jimmunol.170.5.2269
Yuan, H. & Silberstein, S. D. Histamine and migraine. Headache 58, 184–193 (2018).
pubmed: 28862769
doi: 10.1111/head.13164
Del Valle, J. & Gantz, I. Novel insights into histamine H2 receptor biology. Am. J. Physiol. 273, G987–G996 (1997).
pubmed: 9374694
Yoshimoto, R. et al. Therapeutic potential of histamine H3 receptor agonist for the treatment of obesity and diabetes mellitus. Proc. Natl Acad. Sci. USA 103, 13866–13871 (2006).
pubmed: 16954192
pmcid: 1560086
doi: 10.1073/pnas.0506104103
Liu, Y. et al. Visualization of the activation of the histamine H3 receptor (H3R) using novel fluorescence resonance energy transfer biosensors and their potential application to the study of H3R pharmacology. FEBS J. 285, 2319–2336 (2018).
pubmed: 29701013
doi: 10.1111/febs.14484
O’Reilly, M. et al. Identification of a histamine H4 receptor on human eosinophils-role in eosinophil chemotaxis. J. Recept Signal Transduct. Res. 22, 431–448 (2002).
pubmed: 12503632
doi: 10.1081/RRS-120014612
Zampeli, E. & Tiligada, E. The role of histamine H4 receptor in immune and inflammatory disorders. Br. J. Pharm. 157, 24–33 (2009).
doi: 10.1111/j.1476-5381.2009.00151.x
Jemima, E. A., Prema, A. & Thangam, E. B. Functional characterization of histamine H4 receptor on human mast cells. Mol. Immunol. 62, 19–28 (2014).
pubmed: 24934979
doi: 10.1016/j.molimm.2014.05.007
Shimamura, T. et al. Structure of the human histamine H1 receptor complex with doxepin. Nature 475, 65–70 (2011).
pubmed: 21697825
pmcid: 3131495
doi: 10.1038/nature10236
Robertson, M. J. et al. Structure determination of inactive-state GPCRs with a universal nanobody. Nat. Struct. Mol. Biol. 29, 1188–1195 (2022).
pubmed: 36396979
doi: 10.1038/s41594-022-00859-8
Peng, X. et al. Structural basis for recognition of antihistamine drug by human histamine receptor. Nat. Commun. 13, 6105 (2022).
pubmed: 36243875
pmcid: 9569329
doi: 10.1038/s41467-022-33880-y
Im, D. et al. Structural insights into the agonists binding and receptor selectivity of human histamine H(4) receptor. Nat. Commun. 14, 6538 (2023).
pubmed: 37863901
pmcid: 10589313
doi: 10.1038/s41467-023-42260-z
Wang, C. et al. Measurement and control of quasiparticle dynamics in a superconducting qubit. Nat. Commun. 5, 5836 (2014).
pubmed: 25518969
doi: 10.1038/ncomms6836
Xia, R. et al. Structural basis of ligand recognition and design of antihistamines targeting histamine H4 receptor. Nat. Commun. 15, 2493 (2024).
pubmed: 38509098
pmcid: 10954740
doi: 10.1038/s41467-024-46840-5
Xia, R. X. et al. Cryo-EM structure of the human histamine H-1 receptor/G(q) complex. Nat. Commun. 12, 2086 (2021).
pubmed: 33828102
pmcid: 8027608
doi: 10.1038/s41467-021-22427-2
Hua, T. et al. Crystal structures of agonist-bound human cannabinoid receptor CB1. Nature 547, 468 (2017).
pubmed: 28678776
pmcid: 5793864
doi: 10.1038/nature23272
Carrión-Antolí, A. et al. Antioxidant systems and quality in sweet cherries are improved by preharvest GABA treatments leading to delay postharvest senescence. Int. J. Mol. Sci. 25, 260 (2023).
pubmed: 38203428
pmcid: 10779314
doi: 10.3390/ijms25010260
Zhuang, Y. et al. Structural insights into the human D1 and D2 dopamine receptor signaling complexes. Cell 184, 931–942.e18 (2021).
pubmed: 33571431
pmcid: 8215686
doi: 10.1016/j.cell.2021.01.027
Duan, J. et al. Cryo-EM structure of an activated VIP1 receptor-G protein complex revealed by a NanoBiT tethering strategy. Nat. Commun. 11, 4121 (2020).
pubmed: 32807782
pmcid: 7431577
doi: 10.1038/s41467-020-17933-8
Qi, X. et al. Cryo-EM structure of oxysterol-bound human smoothened coupled to a heterotrimeric Gi. Nature 571, 279–283 (2019).
pubmed: 31168089
pmcid: 6777001
doi: 10.1038/s41586-019-1286-0
Garcia-Nafria, J., Nehme, R., Edwards, P. C. & Tate, C. G. Cryo-EM structure of the serotonin 5-HT1B receptor coupled to heterotrimeric Go. Nature 558, 620–623 (2018).
pubmed: 29925951
pmcid: 6027989
doi: 10.1038/s41586-018-0241-9
Kim, K. et al. Structure of a hallucinogen-activated Gq-coupled 5-HT2A serotonin receptor. Cell 182, 1574–1588.e19 (2020).
pubmed: 32946782
pmcid: 7593816
doi: 10.1016/j.cell.2020.08.024
Rasmussen, S. G. et al. Crystal structure of the beta2 adrenergic receptor-Gs protein complex. Nature 477, 549–555 (2011).
pubmed: 21772288
pmcid: 3184188
doi: 10.1038/nature10361
Koehl, A. et al. Structure of the μ-opioid receptor-Gi protein complex. Nature 558, 547–552 (2018).
pubmed: 29899455
pmcid: 6317904
doi: 10.1038/s41586-018-0219-7
Zheng, S. Q. et al. MotionCor2: anisotropic correction of beam-induced motion for improved cryo-electron microscopy. Nat. Methods 14, 331–332 (2017).
pubmed: 28250466
pmcid: 5494038
doi: 10.1038/nmeth.4193
Zhang, K. Gctf: real-time CTF determination and correction. J. Struct. Biol. 193, 1–12 (2016).
pubmed: 26592709
pmcid: 4711343
doi: 10.1016/j.jsb.2015.11.003
Zivanov, J. et al. New tools for automated high-resolution cryo-EM structure determination in RELION-3. Elife 7, e42166 (2018).
pubmed: 30412051
pmcid: 6250425
doi: 10.7554/eLife.42166
Mao, C. et al. Unsaturated bond recognition leads to biased signal in a fatty acid receptor. Science 380, eadd6220 (2023).
pubmed: 36862765
doi: 10.1126/science.add6220
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).
pubmed: 18351591
doi: 10.1002/jcc.20945
Huang, J. et al. CHARMM36m: an improved force field for folded and intrinsically disordered proteins. Nat. Methods 14, 71–73 (2017).
pubmed: 27819658
doi: 10.1038/nmeth.4067
Van Der Spoel, D. et al. GROMACS: fast, flexible, and free. J. Comput. Chem. 26, 1701–1718 (2005).
pubmed: 16211538
doi: 10.1002/jcc.20291
Xiao, P. et al. Tethered peptide activation mechanism of the adhesion GPCRs ADGRG2 and ADGRG4. Nature 604, 771–778 (2022).
pubmed: 35418677
doi: 10.1038/s41586-022-04590-8
Yang, F. et al. Structure, function and pharmacology of human itch receptor complexes. Nature 600, 164–169 (2021).
pubmed: 34789875
doi: 10.1038/s41586-021-04077-y