Hinge region mediates signal transmission of luteinizing hormone and chorionic gonadotropin receptor
Luteinizing hormone-choriogonadotropin receptor (LHCGR), a class A G protein-coupled receptor (GPCR), plays a pivotal role in the maturation of reproductive organs and embryonic development. Compared with other GPCRs, the subfamily of LHCGR has a large extracellular domain (ECD) to interact with gly...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-01-01
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| Series: | Computational and Structural Biotechnology Journal |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2001037022005335 |
| _version_ | 1797978145982251008 |
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| author | Xinheng He Jia Duan Yujie Ji Lifen Zhao Hualiang Jiang Yi Jiang H. Eric Xu Xi Cheng |
| author_facet | Xinheng He Jia Duan Yujie Ji Lifen Zhao Hualiang Jiang Yi Jiang H. Eric Xu Xi Cheng |
| author_sort | Xinheng He |
| collection | DOAJ |
| description | Luteinizing hormone-choriogonadotropin receptor (LHCGR), a class A G protein-coupled receptor (GPCR), plays a pivotal role in the maturation of reproductive organs and embryonic development. Compared with other GPCRs, the subfamily of LHCGR has a large extracellular domain (ECD) to interact with glycoprotein hormones. A unique hinge region connects the ECD and transmembrane domain (TMD) to transfer the activation signal. However, the signal transmission mechanism remains largely unknown. Here, both molecular dynamics simulation and evolutional analysis were applied to explore the effect of the hinge region on signal transmission. The glycoprotein hormone determined specific hinge region conformations, including the position of a long hinge loop and the ECD-TMD interface. With the hormone, the hinge region showed a characteristic rotation and displayed an active-like conformational landscape of the ECD-TMD interface with an extended TMD. The active-like hinge region conformation transduces the hormone binding signal downwards from ECD to TMD. The relationship between the hinge region and the intracelluar G protein-binding pocket was also inferred. The hinge region-mediated signal transmission mechanism offers a deeper understanding of LHCGR and provides insights into the elucidation of GPCR activation. |
| first_indexed | 2024-04-11T05:18:17Z |
| format | Article |
| id | doaj.art-49f13917d5154dceb7b67fe2dfc95d62 |
| institution | Directory Open Access Journal |
| issn | 2001-0370 |
| language | English |
| last_indexed | 2024-04-11T05:18:17Z |
| publishDate | 2022-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Computational and Structural Biotechnology Journal |
| spelling | doaj.art-49f13917d5154dceb7b67fe2dfc95d622022-12-24T04:55:19ZengElsevierComputational and Structural Biotechnology Journal2001-03702022-01-012065036511Hinge region mediates signal transmission of luteinizing hormone and chorionic gonadotropin receptorXinheng He0Jia Duan1Yujie Ji2Lifen Zhao3Hualiang Jiang4Yi Jiang5H. Eric Xu6Xi Cheng7State Key Laboratory of Drug Research and CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China; University of Chinese Academy of Sciences, Beijing, ChinaState Key Laboratory of Drug Research and CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China; University of Chinese Academy of Sciences, Beijing, ChinaState Key Laboratory of Drug Research and CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China; University of Chinese Academy of Sciences, Beijing, ChinaState Key Laboratory of Drug Research and CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, ChinaState Key Laboratory of Drug Research and CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China; University of Chinese Academy of Sciences, Beijing, China; School of Pharmaceutical Science and Technology, Hangzhou Institute of Advanced Study, Hangzhou, China; School of Life Science and Technology, ShanghaiTech University, Shanghai, China; Lingang Laboratory, Shanghai, ChinaSchool of Life Science and Technology, ShanghaiTech University, Shanghai, China; Lingang Laboratory, Shanghai, China; Corresponding authors at: State Key Laboratory of Drug Research and CAS Key Laboratory of Receptor Research and, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.State Key Laboratory of Drug Research and CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China; University of Chinese Academy of Sciences, Beijing, China; Corresponding authors at: State Key Laboratory of Drug Research and CAS Key Laboratory of Receptor Research and, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.State Key Laboratory of Drug Research and CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China; University of Chinese Academy of Sciences, Beijing, China; School of Pharmaceutical Science and Technology, Hangzhou Institute of Advanced Study, Hangzhou, China; Corresponding authors at: State Key Laboratory of Drug Research and CAS Key Laboratory of Receptor Research and, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.Luteinizing hormone-choriogonadotropin receptor (LHCGR), a class A G protein-coupled receptor (GPCR), plays a pivotal role in the maturation of reproductive organs and embryonic development. Compared with other GPCRs, the subfamily of LHCGR has a large extracellular domain (ECD) to interact with glycoprotein hormones. A unique hinge region connects the ECD and transmembrane domain (TMD) to transfer the activation signal. However, the signal transmission mechanism remains largely unknown. Here, both molecular dynamics simulation and evolutional analysis were applied to explore the effect of the hinge region on signal transmission. The glycoprotein hormone determined specific hinge region conformations, including the position of a long hinge loop and the ECD-TMD interface. With the hormone, the hinge region showed a characteristic rotation and displayed an active-like conformational landscape of the ECD-TMD interface with an extended TMD. The active-like hinge region conformation transduces the hormone binding signal downwards from ECD to TMD. The relationship between the hinge region and the intracelluar G protein-binding pocket was also inferred. The hinge region-mediated signal transmission mechanism offers a deeper understanding of LHCGR and provides insights into the elucidation of GPCR activation.http://www.sciencedirect.com/science/article/pii/S2001037022005335Glycoprotein hormone receptorsG protein-coupled receptorsMolecular dynamics simulationProtein dynamicsEvolutionary analysis |
| spellingShingle | Xinheng He Jia Duan Yujie Ji Lifen Zhao Hualiang Jiang Yi Jiang H. Eric Xu Xi Cheng Hinge region mediates signal transmission of luteinizing hormone and chorionic gonadotropin receptor Computational and Structural Biotechnology Journal Glycoprotein hormone receptors G protein-coupled receptors Molecular dynamics simulation Protein dynamics Evolutionary analysis |
| title | Hinge region mediates signal transmission of luteinizing hormone and chorionic gonadotropin receptor |
| title_full | Hinge region mediates signal transmission of luteinizing hormone and chorionic gonadotropin receptor |
| title_fullStr | Hinge region mediates signal transmission of luteinizing hormone and chorionic gonadotropin receptor |
| title_full_unstemmed | Hinge region mediates signal transmission of luteinizing hormone and chorionic gonadotropin receptor |
| title_short | Hinge region mediates signal transmission of luteinizing hormone and chorionic gonadotropin receptor |
| title_sort | hinge region mediates signal transmission of luteinizing hormone and chorionic gonadotropin receptor |
| topic | Glycoprotein hormone receptors G protein-coupled receptors Molecular dynamics simulation Protein dynamics Evolutionary analysis |
| url | http://www.sciencedirect.com/science/article/pii/S2001037022005335 |
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