Melatonin receptor structures shed new light on melatonin research

被引:43
作者
Cecon, Erika [1 ]
Liu, Lei [1 ,2 ]
Jockers, Ralf [1 ]
机构
[1] Univ Paris, Inst Cochin, CNRS, INSERM, 22 Rue Mechain, F-75014 Paris, France
[2] Huazhong Univ Sci & Technol, Cellular Signaling Lab, Int Res Ctr Sensory Biol & Technol MOST, Key Lab Mol Biophys,Minist Educ,Sch Life Sci & Te, Wuhan, Hubei, Peoples R China
关键词
crystal structure; dimers; GPCR; melatonin; G-PROTEIN; MT1; DIMERS; LIGANDS; CLONING; RETINA; DESIGN; POTENT;
D O I
10.1111/jpi.12606
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The tryptophan derivative melatonin is an evolutionary old molecule that is involved in a pleiotropy of physiological functions. In humans, age-related decline of circulating melatonin levels and/or dysregulation of its circadian synthesis pattern have been associated with several disorders and disease states. Several molecular targets have been proposed for melatonin since its discovery, in 1959. Among them, melatonin MT1 and MT2 receptors are the best characterized melatonin targets, mediating melatonin effects in a variety of tissues. They belong to the superfamily of G protein-coupled receptors. Two back-to-back articles published in the "Nature" Journal earlier this year present the first crystal structures of the human MT1 and MT2 in its inactive states. Here, we will briefly outline the discovery path of melatonin receptors until their structural elucidation and discuss how these new findings will guide future research toward a better understanding of their function and rational drug design.
引用
收藏
页数:6
相关论文
共 33 条
[1]   Monitoring of ligand-independent dimerization and ligand-induced conformational changes of melatonin receptors in living cells by bioluminescence resonance energy transfer [J].
Ayoub, MA ;
Couturier, C ;
Lucas-Meunier, E ;
Angers, S ;
Fossier, P ;
Bouvier, M ;
Jockers, R .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (24) :21522-21528
[2]   Heteromeric MT1/MT2 Melatonin Receptors Modulate Photoreceptor Function [J].
Baba, Kenkichi ;
Benleulmi-Chaachoua, Abla ;
Journe, Anne-Sophie ;
Kamal, Maud ;
Guillaume, Jean-Luc ;
Dussaud, Sebastien ;
Gbahou, Florence ;
Yettou, Katia ;
Liu, Cuimei ;
Contreras-Alcantara, Susana ;
Jockers, Ralf ;
Tosini, Gianluca .
SCIENCE SIGNALING, 2013, 6 (296)
[3]  
Cecon E., 2017, BRIT J PHARMACOL, V175, P3263
[4]  
Clement N, 2017, BRIT J PHARMACOL, V175, P3281
[5]   Design and synthesis of naphthalenic dimers as selective MT1 melatoninergic ligands [J].
Descamps-François, C ;
Yous, S ;
Chavatte, P ;
Audinot, V ;
Bonnaud, A ;
Boutin, JA ;
Delagrange, P ;
Bennejean, C ;
Renard, P ;
Lesieur, D .
JOURNAL OF MEDICINAL CHEMISTRY, 2003, 46 (07) :1127-1129
[6]   Description of the constitutive activity of cloned human melatonin receptors hMT1 and hMT2 and discovery of inverse agonists [J].
Devavry, Severine ;
Legros, Celine ;
Brasseur, Chantal ;
Delagrange, Philippe ;
Spadoni, Gilberto ;
Cohen, William ;
Malpaux, Benoit ;
Boutin, Jean A. ;
Nosjean, Olivier .
JOURNAL OF PINEAL RESEARCH, 2012, 53 (01) :29-37
[7]   Allosteric coupling from G protein to the agonist-binding pocket in GPCRs [J].
DeVree, Brian T. ;
Mahoney, Jacob P. ;
Velez-Ruiz, Gisselle A. ;
Rasmussen, Soren G. F. ;
Kuszak, Adam J. ;
Edwald, Elin ;
Fung, Juan-Jose ;
Manglik, Aashish ;
Masureel, Matthieu ;
Du, Yang ;
Matt, Rachel A. ;
Pardon, Els ;
Steyaert, Jan ;
Kobilka, Brian K. ;
Sunahara, Roger K. .
NATURE, 2016, 535 (7610) :182-+
[8]   International Union of Basic and Clinical Pharmacology. LXXV. Nomenclature, Classification, and Pharmacology of G Protein-Coupled Melatonin Receptors [J].
Dubocovich, Margarita L. ;
Delagrange, Philippe ;
Krause, Diana N. ;
Sugden, David ;
Cardinali, Daniel P. ;
Olcese, James .
PHARMACOLOGICAL REVIEWS, 2010, 62 (03) :343-380
[9]   MELATONIN IS A POTENT MODULATOR OF DOPAMINE RELEASE IN THE RETINA [J].
DUBOCOVICH, ML .
NATURE, 1983, 306 (5945) :782-784
[10]   Melatonin receptor antagonists that differentiate between the human Mel(1a), and Mel(1b) recombinant subtypes are used to assess the pharmacological profile of the rabbit retina ML(1) presynaptic heteroreceptor [J].
Dubocovich, ML ;
Masana, MI ;
Iacob, S ;
Sauri, DM .
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY, 1997, 355 (03) :365-375