How the ghrelin receptor recognizes the acyl-modified orexigenic hormone.

IF 3.5 3区医学 Q2 NEUROSCIENCES

Frontiers in Molecular Neuroscience Pub Date : 2025-04-07 eCollection Date: 2025-01-01 DOI:10.3389/fnmol.2025.1549366

Yuki Shiimura, Masayasu Kojima, Takahiro Sato

引用次数: 0

Abstract

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.

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生长素受体如何识别酰基修饰的促氧激素。

Ghrelin于1999年被发现，是生长激素促分泌受体（现称为Ghrelin受体）的内源性配体，是一种具有多种生理活性的肽激素，如刺激生长激素释放、增加食欲、脂肪积累、体温调节、心脏保护等。胃饥饿素的一个显著特征是需要经过辛烷酰化（一种特殊的酰基修饰）才能发挥其生物活性。虽然胃饥饿素受体特异性地识别这种修饰，但其潜在的分子机制几十年来一直不清楚。在饥饿素发现25 年后，结构生物学的最新进展促进了这种识别机制的阐明。本文综述了胃饥饿素辛烷化的结构基础，特别强调了胃饥饿素受体识别这种酰基修饰激素的机制。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Frontiers in Molecular Neuroscience NEUROSCIENCES-

CiteScore

5.70

自引率

2.10%

发文量

669

审稿时长

14 weeks

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.