Chemoproteomics identifies protein ligands for monoacylglycerol lipids
Abstract 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 endocanna...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-07-01
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| Series: | Communications Chemistry |
| Online Access: | https://doi.org/10.1038/s42004-025-01589-w |
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| author | Karthik Shanbhag Amol B. Mhetre Ojal Saharan Archit Devarajan Anisha Rai M. S. Madhusudhan Harinath Chakrapani Siddhesh S. Kamat |
| author_facet | Karthik Shanbhag Amol B. Mhetre Ojal Saharan Archit Devarajan Anisha Rai M. S. Madhusudhan Harinath Chakrapani Siddhesh S. Kamat |
| author_sort | Karthik Shanbhag |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-5886b80d4f2f4cb7b3c39287c934e0fa |
| institution | Kabale University |
| issn | 2399-3669 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Chemistry |
| spelling | doaj-art-5886b80d4f2f4cb7b3c39287c934e0fa2025-08-20T03:37:20ZengNature PortfolioCommunications Chemistry2399-36692025-07-018111310.1038/s42004-025-01589-wChemoproteomics identifies protein ligands for monoacylglycerol lipidsKarthik Shanbhag0Amol B. Mhetre1Ojal Saharan2Archit Devarajan3Anisha Rai4M. S. Madhusudhan5Harinath Chakrapani6Siddhesh S. Kamat7Department of Biology, Indian Institute of Science Education and ResearchDepartment of Biology, Indian Institute of Science Education and ResearchDepartment of Biology, Indian Institute of Science Education and ResearchDepartment of Biology, Indian Institute of Science Education and ResearchDepartment of Biology, Indian Institute of Science Education and ResearchDepartment of Biology, Indian Institute of Science Education and ResearchDepartment of Chemistry, Indian Institute of Science Education and ResearchDepartment of Biology, Indian Institute of Science Education and ResearchAbstract 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.https://doi.org/10.1038/s42004-025-01589-w |
| spellingShingle | Karthik Shanbhag Amol B. Mhetre Ojal Saharan Archit Devarajan Anisha Rai M. S. Madhusudhan Harinath Chakrapani Siddhesh S. Kamat Chemoproteomics identifies protein ligands for monoacylglycerol lipids Communications Chemistry |
| title | Chemoproteomics identifies protein ligands for monoacylglycerol lipids |
| title_full | Chemoproteomics identifies protein ligands for monoacylglycerol lipids |
| title_fullStr | Chemoproteomics identifies protein ligands for monoacylglycerol lipids |
| title_full_unstemmed | Chemoproteomics identifies protein ligands for monoacylglycerol lipids |
| title_short | Chemoproteomics identifies protein ligands for monoacylglycerol lipids |
| title_sort | chemoproteomics identifies protein ligands for monoacylglycerol lipids |
| url | https://doi.org/10.1038/s42004-025-01589-w |
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