{"title":"生长素受体如何识别酰基修饰的促氧激素。","authors":"Yuki Shiimura, Masayasu Kojima, Takahiro Sato","doi":"10.3389/fnmol.2025.1549366","DOIUrl":null,"url":null,"abstract":"<p><p>Ghrelin, discovered in 1999 as an endogenous ligand of the growth hormone secretagogue receptor (now known as the ghrelin receptor), is a peptide hormone with diverse physiological activities, such as stimulation of growth hormone release, increased appetite, fat accumulation, thermoregulation, and cardioprotection. As a distinctive feature, ghrelin needs to undergo octanoylation, a specific acyl modification, to exert its biological activities. Although the ghrelin receptor specifically recognizes this modification, the underlying molecular mechanism had remained unclear for decades. Recent advancements in structural biology have facilitated the elucidation of this recognition mechanism 25 years after ghrelin's discovery. This review highlights the structural basis of ghrelin octanoylation, particularly emphasizing the mechanism by which the ghrelin receptor recognizes this acyl-modified hormone.</p>","PeriodicalId":12630,"journal":{"name":"Frontiers in Molecular Neuroscience","volume":"18 ","pages":"1549366"},"PeriodicalIF":3.5000,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12009760/pdf/","citationCount":"0","resultStr":"{\"title\":\"How the ghrelin receptor recognizes the acyl-modified orexigenic hormone.\",\"authors\":\"Yuki Shiimura, Masayasu Kojima, Takahiro Sato\",\"doi\":\"10.3389/fnmol.2025.1549366\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Ghrelin, discovered in 1999 as an endogenous ligand of the growth hormone secretagogue receptor (now known as the ghrelin receptor), is a peptide hormone with diverse physiological activities, such as stimulation of growth hormone release, increased appetite, fat accumulation, thermoregulation, and cardioprotection. As a distinctive feature, ghrelin needs to undergo octanoylation, a specific acyl modification, to exert its biological activities. Although the ghrelin receptor specifically recognizes this modification, the underlying molecular mechanism had remained unclear for decades. Recent advancements in structural biology have facilitated the elucidation of this recognition mechanism 25 years after ghrelin's discovery. This review highlights the structural basis of ghrelin octanoylation, particularly emphasizing the mechanism by which the ghrelin receptor recognizes this acyl-modified hormone.</p>\",\"PeriodicalId\":12630,\"journal\":{\"name\":\"Frontiers in Molecular Neuroscience\",\"volume\":\"18 \",\"pages\":\"1549366\"},\"PeriodicalIF\":3.5000,\"publicationDate\":\"2025-04-07\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12009760/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Frontiers in Molecular Neuroscience\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.3389/fnmol.2025.1549366\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q2\",\"JCRName\":\"NEUROSCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in Molecular Neuroscience","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3389/fnmol.2025.1549366","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
How the ghrelin receptor recognizes the acyl-modified orexigenic hormone.
Ghrelin, discovered in 1999 as an endogenous ligand of the growth hormone secretagogue receptor (now known as the ghrelin receptor), is a peptide hormone with diverse physiological activities, such as stimulation of growth hormone release, increased appetite, fat accumulation, thermoregulation, and cardioprotection. As a distinctive feature, ghrelin needs to undergo octanoylation, a specific acyl modification, to exert its biological activities. Although the ghrelin receptor specifically recognizes this modification, the underlying molecular mechanism had remained unclear for decades. Recent advancements in structural biology have facilitated the elucidation of this recognition mechanism 25 years after ghrelin's discovery. This review highlights the structural basis of ghrelin octanoylation, particularly emphasizing the mechanism by which the ghrelin receptor recognizes this acyl-modified hormone.
期刊介绍：
Frontiers in Molecular Neuroscience is a first-tier electronic journal devoted to identifying key molecules, as well as their functions and interactions, that underlie the structure, design and function of the brain across all levels. The scope of our journal encompasses synaptic and cellular proteins, coding and non-coding RNA, and molecular mechanisms regulating cellular and dendritic RNA translation. In recent years, a plethora of new cellular and synaptic players have been identified from reduced systems, such as neuronal cultures, but the relevance of these molecules in terms of cellular and synaptic function and plasticity in the living brain and its circuits has not been validated. The effects of spine growth and density observed using gene products identified from in vitro work are frequently not reproduced in vivo. Our journal is particularly interested in studies on genetically engineered model organisms (C. elegans, Drosophila, mouse), in which alterations in key molecules underlying cellular and synaptic function and plasticity produce defined anatomical, physiological and behavioral changes. In the mouse, genetic alterations limited to particular neural circuits (olfactory bulb, motor cortex, cortical layers, hippocampal subfields, cerebellum), preferably regulated in time and on demand, are of special interest, as they sidestep potential compensatory developmental effects.
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