化学蛋白质组学鉴定单酰基甘油脂的蛋白质配体。

IF 6.2 2区 化学 Q1 CHEMISTRY, MULTIDISCIPLINARY
Karthik Shanbhag, Amol B Mhetre, Ojal Saharan, Archit Devarajan, Anisha Rai, M S Madhusudhan, Harinath Chakrapani, Siddhesh S Kamat
{"title":"化学蛋白质组学鉴定单酰基甘油脂的蛋白质配体。","authors":"Karthik Shanbhag, Amol B Mhetre, Ojal Saharan, Archit Devarajan, Anisha Rai, M S Madhusudhan, Harinath Chakrapani, Siddhesh S Kamat","doi":"10.1038/s42004-025-01589-w","DOIUrl":null,"url":null,"abstract":"<p><p>Signaling lipids are important hormone-like biomolecules that regulate many physiological processes in humans. However, a significant number of them still remain poorly characterized, despite their direct association to human diseases. While the signaling pathways regulated by the endocannabinoid 2-arachidonoyl-glycerol in mammals are extensively characterized, the same cannot be said about other members of the monoacylglycerol (MAG) family of signaling lipids. Here, we report the synthesis of a bifunctional MAG probe, containing a photoreactive group and an alkyne handle. Using established chemoproteomics approaches coupled to bioorthogonal chemistry, we profile this bifunctional MAG probe in mouse brain and mammalian cell proteomes, and identify hitherto unknown protein ligands for MAG lipids. Finally, we find that the neuronal calcium sensor Hippocalcin is indeed a putative MAG protein ligand, and show that MAG lipids may have a role to play in calcium sensing and downstream signaling in the mammalian brain.</p>","PeriodicalId":10529,"journal":{"name":"Communications Chemistry","volume":"8 1","pages":"197"},"PeriodicalIF":6.2000,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12227648/pdf/","citationCount":"0","resultStr":"{\"title\":\"Chemoproteomics identifies protein ligands for monoacylglycerol lipids.\",\"authors\":\"Karthik Shanbhag, Amol B Mhetre, Ojal Saharan, Archit Devarajan, Anisha Rai, M S Madhusudhan, Harinath Chakrapani, Siddhesh S Kamat\",\"doi\":\"10.1038/s42004-025-01589-w\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Signaling lipids are important hormone-like biomolecules that regulate many physiological processes in humans. However, a significant number of them still remain poorly characterized, despite their direct association to human diseases. While the signaling pathways regulated by the endocannabinoid 2-arachidonoyl-glycerol in mammals are extensively characterized, the same cannot be said about other members of the monoacylglycerol (MAG) family of signaling lipids. Here, we report the synthesis of a bifunctional MAG probe, containing a photoreactive group and an alkyne handle. Using established chemoproteomics approaches coupled to bioorthogonal chemistry, we profile this bifunctional MAG probe in mouse brain and mammalian cell proteomes, and identify hitherto unknown protein ligands for MAG lipids. Finally, we find that the neuronal calcium sensor Hippocalcin is indeed a putative MAG protein ligand, and show that MAG lipids may have a role to play in calcium sensing and downstream signaling in the mammalian brain.</p>\",\"PeriodicalId\":10529,\"journal\":{\"name\":\"Communications Chemistry\",\"volume\":\"8 1\",\"pages\":\"197\"},\"PeriodicalIF\":6.2000,\"publicationDate\":\"2025-07-04\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12227648/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Communications Chemistry\",\"FirstCategoryId\":\"92\",\"ListUrlMain\":\"https://doi.org/10.1038/s42004-025-01589-w\",\"RegionNum\":2,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, MULTIDISCIPLINARY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Communications Chemistry","FirstCategoryId":"92","ListUrlMain":"https://doi.org/10.1038/s42004-025-01589-w","RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
引用次数: 0

摘要

信号脂质是调节人体许多生理过程的重要激素类生物分子。然而,尽管它们与人类疾病有直接联系,但它们中的相当一部分仍然缺乏特征。虽然哺乳动物内源性大麻素2-花生四烯醇-甘油调节的信号通路被广泛表征,但单酰基甘油(MAG)信号脂类家族的其他成员却没有被广泛表征。在这里,我们报道了一种双功能MAG探针的合成,它包含一个光反应基团和一个炔柄。利用已建立的化学蛋白质组学方法与生物正交化学相结合,我们在小鼠脑和哺乳动物细胞蛋白质组中分析了这种双功能MAG探针,并鉴定了迄今为止未知的MAG脂质蛋白质配体。最后,我们发现神经元钙传感器Hippocalcin确实是一种假定的MAG蛋白配体,并表明MAG脂质可能在哺乳动物大脑中的钙感知和下游信号传导中发挥作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Chemoproteomics identifies protein ligands for monoacylglycerol lipids.

Signaling lipids are important hormone-like biomolecules that regulate many physiological processes in humans. However, a significant number of them still remain poorly characterized, despite their direct association to human diseases. While the signaling pathways regulated by the endocannabinoid 2-arachidonoyl-glycerol in mammals are extensively characterized, the same cannot be said about other members of the monoacylglycerol (MAG) family of signaling lipids. Here, we report the synthesis of a bifunctional MAG probe, containing a photoreactive group and an alkyne handle. Using established chemoproteomics approaches coupled to bioorthogonal chemistry, we profile this bifunctional MAG probe in mouse brain and mammalian cell proteomes, and identify hitherto unknown protein ligands for MAG lipids. Finally, we find that the neuronal calcium sensor Hippocalcin is indeed a putative MAG protein ligand, and show that MAG lipids may have a role to play in calcium sensing and downstream signaling in the mammalian brain.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Communications Chemistry
Communications Chemistry Chemistry-General Chemistry
CiteScore
7.70
自引率
1.70%
发文量
146
审稿时长
13 weeks
期刊介绍: Communications Chemistry is an open access journal from Nature Research publishing high-quality research, reviews and commentary in all areas of the chemical sciences. Research papers published by the journal represent significant advances bringing new chemical insight to a specialized area of research. We also aim to provide a community forum for issues of importance to all chemists, regardless of sub-discipline.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信