Post-Translational Modifications of G Protein–Coupled Receptors Revealed by Proteomics and Structural Biology
G protein–coupled receptors (GPCRs) are a protein superfamily comprising >800 members that regulate numerous cellular and physiologic responses. GPCRs represent the largest class of therapeutic targets with implications in various diseases. Although advances in GPCR structural and pharmacolog...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-03-01
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| Series: | Frontiers in Chemistry |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fchem.2022.843502/full |
| _version_ | 1818317488129048576 |
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| author | Bingjie Zhang Shanshan Li Wenqing Shui Wenqing Shui |
| author_facet | Bingjie Zhang Shanshan Li Wenqing Shui Wenqing Shui |
| author_sort | Bingjie Zhang |
| collection | DOAJ |
| description | G protein–coupled receptors (GPCRs) are a protein superfamily comprising >800 members that regulate numerous cellular and physiologic responses. GPCRs represent the largest class of therapeutic targets with implications in various diseases. Although advances in GPCR structural and pharmacological research have significantly improved our knowledge of GPCR signaling mechanisms, mapping diverse post-translational modifications (PTMs) of GPCR proteins and understanding their regulatory roles have received much less attention. Mass spectrometry-based proteomics has become the most popular technology for profiling protein PTMs in a systematic manner. Herein we provide an overview of PTM types, locations, crosstalk and dynamic regulation for different GPCRs that are characterized using proteomic and/or biochemical approaches. Our main focus is on glycosylation, phosphorylation, ubiquitination and palmitoylation that are known to modulate receptor folding, biosynthesis, trafficking, dimerization and signaling. Furthermore, we discuss the locations of specific PTM sites in the structure of a given GPCR and its signaling complex to highlight the importance of PTM regulation in the molecular basis of GPCRs, which may shed new light on structure-based drug discovery. |
| first_indexed | 2024-12-13T09:38:07Z |
| format | Article |
| id | doaj.art-302ae59179c04fc4bfb5c98b463408bb |
| institution | Directory Open Access Journal |
| issn | 2296-2646 |
| language | English |
| last_indexed | 2024-12-13T09:38:07Z |
| publishDate | 2022-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Chemistry |
| spelling | doaj.art-302ae59179c04fc4bfb5c98b463408bb2022-12-21T23:52:16ZengFrontiers Media S.A.Frontiers in Chemistry2296-26462022-03-011010.3389/fchem.2022.843502843502Post-Translational Modifications of G Protein–Coupled Receptors Revealed by Proteomics and Structural BiologyBingjie Zhang0Shanshan Li1Wenqing Shui2Wenqing Shui3iHuman Institute, ShanghaiTech University, Shanghai, ChinaiHuman Institute, ShanghaiTech University, Shanghai, ChinaiHuman Institute, ShanghaiTech University, Shanghai, ChinaSchool of Life Science and Technology, ShanghaiTech University, Shanghai, ChinaG protein–coupled receptors (GPCRs) are a protein superfamily comprising >800 members that regulate numerous cellular and physiologic responses. GPCRs represent the largest class of therapeutic targets with implications in various diseases. Although advances in GPCR structural and pharmacological research have significantly improved our knowledge of GPCR signaling mechanisms, mapping diverse post-translational modifications (PTMs) of GPCR proteins and understanding their regulatory roles have received much less attention. Mass spectrometry-based proteomics has become the most popular technology for profiling protein PTMs in a systematic manner. Herein we provide an overview of PTM types, locations, crosstalk and dynamic regulation for different GPCRs that are characterized using proteomic and/or biochemical approaches. Our main focus is on glycosylation, phosphorylation, ubiquitination and palmitoylation that are known to modulate receptor folding, biosynthesis, trafficking, dimerization and signaling. Furthermore, we discuss the locations of specific PTM sites in the structure of a given GPCR and its signaling complex to highlight the importance of PTM regulation in the molecular basis of GPCRs, which may shed new light on structure-based drug discovery.https://www.frontiersin.org/articles/10.3389/fchem.2022.843502/fullG protein couped receptorsmass spectrometry-based proteomicsPost-translational modification (PTM)phosphorylationsignaling regulation |
| spellingShingle | Bingjie Zhang Shanshan Li Wenqing Shui Wenqing Shui Post-Translational Modifications of G Protein–Coupled Receptors Revealed by Proteomics and Structural Biology Frontiers in Chemistry G protein couped receptors mass spectrometry-based proteomics Post-translational modification (PTM) phosphorylation signaling regulation |
| title | Post-Translational Modifications of G Protein–Coupled Receptors Revealed by Proteomics and Structural Biology |
| title_full | Post-Translational Modifications of G Protein–Coupled Receptors Revealed by Proteomics and Structural Biology |
| title_fullStr | Post-Translational Modifications of G Protein–Coupled Receptors Revealed by Proteomics and Structural Biology |
| title_full_unstemmed | Post-Translational Modifications of G Protein–Coupled Receptors Revealed by Proteomics and Structural Biology |
| title_short | Post-Translational Modifications of G Protein–Coupled Receptors Revealed by Proteomics and Structural Biology |
| title_sort | post translational modifications of g protein coupled receptors revealed by proteomics and structural biology |
| topic | G protein couped receptors mass spectrometry-based proteomics Post-translational modification (PTM) phosphorylation signaling regulation |
| url | https://www.frontiersin.org/articles/10.3389/fchem.2022.843502/full |
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