Structure, function and drug discovery of GPCR signaling
Abstract G protein-coupled receptors (GPCRs) are versatile and vital proteins involved in a wide array of physiological processes and responses, such as sensory perception (e.g., vision, taste, and smell), immune response, hormone regulation, and neurotransmission. Their diverse and essential roles...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Springer
2023-12-01
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| Series: | Molecular Biomedicine |
| Online Access: | https://doi.org/10.1186/s43556-023-00156-w |
| _version_ | 1797398229863628800 |
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| author | Lin Cheng Fan Xia Ziyan Li Chenglong Shen Zhiqian Yang Hanlin Hou Suyue Sun Yuying Feng Xihao Yong Xiaowen Tian Hongxi Qin Wei Yan Zhenhua Shao |
| author_facet | Lin Cheng Fan Xia Ziyan Li Chenglong Shen Zhiqian Yang Hanlin Hou Suyue Sun Yuying Feng Xihao Yong Xiaowen Tian Hongxi Qin Wei Yan Zhenhua Shao |
| author_sort | Lin Cheng |
| collection | DOAJ |
| description | Abstract G protein-coupled receptors (GPCRs) are versatile and vital proteins involved in a wide array of physiological processes and responses, such as sensory perception (e.g., vision, taste, and smell), immune response, hormone regulation, and neurotransmission. Their diverse and essential roles in the body make them a significant focus for pharmaceutical research and drug development. Currently, approximately 35% of marketed drugs directly target GPCRs, underscoring their prominence as therapeutic targets. Recent advances in structural biology have substantially deepened our understanding of GPCR activation mechanisms and interactions with G-protein and arrestin signaling pathways. This review offers an in-depth exploration of both traditional and recent methods in GPCR structure analysis. It presents structure-based insights into ligand recognition and receptor activation mechanisms and delves deeper into the mechanisms of canonical and noncanonical signaling pathways downstream of GPCRs. Furthermore, it highlights recent advancements in GPCR-related drug discovery and development. Particular emphasis is placed on GPCR selective drugs, allosteric and biased signaling, polyphamarcology, and antibody drugs. Our goal is to provide researchers with a thorough and updated understanding of GPCR structure determination, signaling pathway investigation, and drug development. This foundation aims to propel forward-thinking therapeutic approaches that target GPCRs, drawing upon the latest insights into GPCR ligand selectivity, activation, and biased signaling mechanisms. |
| first_indexed | 2024-03-09T01:22:39Z |
| format | Article |
| id | doaj.art-9145c1751e7249539653cb0aa973510b |
| institution | Directory Open Access Journal |
| issn | 2662-8651 |
| language | English |
| last_indexed | 2024-03-09T01:22:39Z |
| publishDate | 2023-12-01 |
| publisher | Springer |
| record_format | Article |
| series | Molecular Biomedicine |
| spelling | doaj.art-9145c1751e7249539653cb0aa973510b2023-12-10T12:04:33ZengSpringerMolecular Biomedicine2662-86512023-12-014113910.1186/s43556-023-00156-wStructure, function and drug discovery of GPCR signalingLin Cheng0Fan Xia1Ziyan Li2Chenglong Shen3Zhiqian Yang4Hanlin Hou5Suyue Sun6Yuying Feng7Xihao Yong8Xiaowen Tian9Hongxi Qin10Wei Yan11Zhenhua Shao12Division of Nephrology and Kidney Research Institute, State Key Laboratory of Biotherapy, West China Hospital, Sichuan UniversityDepartment of Neurosurgery, West China Hospital, Sichuan UniversityDivision of Nephrology and Kidney Research Institute, State Key Laboratory of Biotherapy, West China Hospital, Sichuan UniversityDivision of Nephrology and Kidney Research Institute, State Key Laboratory of Biotherapy, West China Hospital, Sichuan UniversityDivision of Nephrology and Kidney Research Institute, State Key Laboratory of Biotherapy, West China Hospital, Sichuan UniversityDivision of Nephrology and Kidney Research Institute, State Key Laboratory of Biotherapy, West China Hospital, Sichuan UniversityDivision of Nephrology and Kidney Research Institute, State Key Laboratory of Biotherapy, West China Hospital, Sichuan UniversityDivision of Nephrology and Kidney Research Institute, State Key Laboratory of Biotherapy, West China Hospital, Sichuan UniversityDivision of Nephrology and Kidney Research Institute, State Key Laboratory of Biotherapy, West China Hospital, Sichuan UniversityDivision of Nephrology and Kidney Research Institute, State Key Laboratory of Biotherapy, West China Hospital, Sichuan UniversityDivision of Nephrology and Kidney Research Institute, State Key Laboratory of Biotherapy, West China Hospital, Sichuan UniversityDivision of Nephrology and Kidney Research Institute, State Key Laboratory of Biotherapy, West China Hospital, Sichuan UniversityDivision of Nephrology and Kidney Research Institute, State Key Laboratory of Biotherapy, West China Hospital, Sichuan UniversityAbstract G protein-coupled receptors (GPCRs) are versatile and vital proteins involved in a wide array of physiological processes and responses, such as sensory perception (e.g., vision, taste, and smell), immune response, hormone regulation, and neurotransmission. Their diverse and essential roles in the body make them a significant focus for pharmaceutical research and drug development. Currently, approximately 35% of marketed drugs directly target GPCRs, underscoring their prominence as therapeutic targets. Recent advances in structural biology have substantially deepened our understanding of GPCR activation mechanisms and interactions with G-protein and arrestin signaling pathways. This review offers an in-depth exploration of both traditional and recent methods in GPCR structure analysis. It presents structure-based insights into ligand recognition and receptor activation mechanisms and delves deeper into the mechanisms of canonical and noncanonical signaling pathways downstream of GPCRs. Furthermore, it highlights recent advancements in GPCR-related drug discovery and development. Particular emphasis is placed on GPCR selective drugs, allosteric and biased signaling, polyphamarcology, and antibody drugs. Our goal is to provide researchers with a thorough and updated understanding of GPCR structure determination, signaling pathway investigation, and drug development. This foundation aims to propel forward-thinking therapeutic approaches that target GPCRs, drawing upon the latest insights into GPCR ligand selectivity, activation, and biased signaling mechanisms.https://doi.org/10.1186/s43556-023-00156-w |
| spellingShingle | Lin Cheng Fan Xia Ziyan Li Chenglong Shen Zhiqian Yang Hanlin Hou Suyue Sun Yuying Feng Xihao Yong Xiaowen Tian Hongxi Qin Wei Yan Zhenhua Shao Structure, function and drug discovery of GPCR signaling Molecular Biomedicine |
| title | Structure, function and drug discovery of GPCR signaling |
| title_full | Structure, function and drug discovery of GPCR signaling |
| title_fullStr | Structure, function and drug discovery of GPCR signaling |
| title_full_unstemmed | Structure, function and drug discovery of GPCR signaling |
| title_short | Structure, function and drug discovery of GPCR signaling |
| title_sort | structure function and drug discovery of gpcr signaling |
| url | https://doi.org/10.1186/s43556-023-00156-w |
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