Melatonin receptor structure and signaling

IF 8.3 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Journal of Pineal Research Pub Date : 2024-04-08 DOI:10.1111/jpi.12952
Hiroyuki H. Okamoto, Erika Cecon, Osamu Nureki, Silvia Rivara, Ralf Jockers
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Abstract

Melatonin (5-methoxy-N-acetyltryptamine) binds with high affinity and specificity to membrane receptors. Several receptor subtypes exist in different species, of which the mammalian MT1 and MT2 receptors are the best-characterized. They are members of the G protein-coupled receptor superfamily, preferentially coupling to Gi/o proteins but also to other G proteins in a cell-context-depending manner. In this review, experts on melatonin receptors will summarize the current state of the field. We briefly report on the discovery and classification of melatonin receptors, then focus on the molecular structure of human MT1 and MT2 receptors and highlight the importance of molecular simulations to identify new ligands and to understand the structural dynamics of these receptors. We then describe the state-of-the-art of the intracellular signaling pathways activated by melatonin receptors and their complexes. Brief statements on the molecular toolbox available for melatonin receptor studies and future perspectives will round-up this review.

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褪黑素受体的结构和信号传导
褪黑素(5-甲氧基-N-乙酰色胺)与膜受体的结合具有高亲和力和特异性。不同物种存在多种受体亚型,其中以哺乳动物的 MT1 和 MT2 受体最为典型。它们是G蛋白偶联受体超家族的成员,优先与Gi/o蛋白偶联,但也会根据细胞环境与其他G蛋白偶联。在本综述中,褪黑激素受体方面的专家将总结该领域的现状。我们将简要报告褪黑激素受体的发现和分类,然后重点介绍人类 MT1 和 MT2 受体的分子结构,并强调分子模拟在确定新配体和了解这些受体的结构动态方面的重要性。然后,我们介绍了由褪黑激素受体及其复合物激活的细胞内信号通路的最新进展。关于可用于褪黑激素受体研究的分子工具箱和未来展望的简要说明将为本综述画上圆满句号。
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来源期刊
Journal of Pineal Research
Journal of Pineal Research 医学-内分泌学与代谢
CiteScore
17.70
自引率
4.90%
发文量
66
审稿时长
1 months
期刊介绍: The Journal of Pineal Research welcomes original scientific research on the pineal gland and melatonin in vertebrates, as well as the biological functions of melatonin in non-vertebrates, plants, and microorganisms. Criteria for publication include scientific importance, novelty, timeliness, and clarity of presentation. The journal considers experimental data that challenge current thinking and welcomes case reports contributing to understanding the pineal gland and melatonin research. Its aim is to serve researchers in all disciplines related to the pineal gland and melatonin.
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