Functional Characterization of the Internal Symmetry of MRAP2 Antiparallel Homodimer
The melanocortin receptors are defined as a series of vital pharmaceutical targets to regulate neuronal appetite and maintain controllable body weight for mammals and teleosts. Melanocortin receptor accessory protein 2 (MRAP2) functions as an essential accessory player that modulates the surface tra...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2021-10-01
|
| Series: | Frontiers in Endocrinology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2021.750797/full |
| _version_ | 1818580665233309696 |
|---|---|
| author | Meng Wang Linyu Pi Xiaowei Lei Lei Li Jing Xu Zhe Kuang Cong Zhang Liang Li Chao Zhang |
| author_facet | Meng Wang Linyu Pi Xiaowei Lei Lei Li Jing Xu Zhe Kuang Cong Zhang Liang Li Chao Zhang |
| author_sort | Meng Wang |
| collection | DOAJ |
| description | The melanocortin receptors are defined as a series of vital pharmaceutical targets to regulate neuronal appetite and maintain controllable body weight for mammals and teleosts. Melanocortin receptor accessory protein 2 (MRAP2) functions as an essential accessory player that modulates the surface translocation and binding to a variety of endogenous or synthetic hormones of central melanocortin-4 receptor (MC4R) signaling. MRAP2 is a single-transmembrane protein and could form a functional symmetric antiparallel homodimer topology. Here, we inverted the N-terminal, transmembrane, and C-terminal domains and generated six distinct conformational variants of the mouse MRAP2 to explore the functional orientations and the internal symmetry of MRAP2 dimers. These remolded MRAP2 mutants showed proper assembly of the antiparallel homodimer and binding to the MC4R, but slightly altered the regulatory profile on the surface expression and the ligand-stimulated cAMP cascades of MC4R. This study elucidated the importance of the orientation of each domain of the single-transmembrane protein and revealed the pharmacological properties of the internal symmetry of the antiparallel homodimer for MRAP2. |
| first_indexed | 2024-12-16T07:21:12Z |
| format | Article |
| id | doaj.art-fa458dfe1a104b9fbff4ab0717e794f3 |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-12-16T07:21:12Z |
| publishDate | 2021-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-fa458dfe1a104b9fbff4ab0717e794f32022-12-21T22:39:39ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922021-10-011210.3389/fendo.2021.750797750797Functional Characterization of the Internal Symmetry of MRAP2 Antiparallel HomodimerMeng Wang0Linyu Pi1Xiaowei Lei2Lei Li3Jing Xu4Zhe Kuang5Cong Zhang6Liang Li7Chao Zhang8Department of Plastic and Reconstructive Surgery, Shanghai Institute of Precision Medicine, Shanghai Ninth People’s Hospital, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Plastic and Reconstructive Surgery, Shanghai Institute of Precision Medicine, Shanghai Ninth People’s Hospital, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaTranslational Medical Center for Stem Cell Therapy and Institute for Regenerative Medicine, Shanghai East Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai, ChinaDepartment of Plastic and Reconstructive Surgery, Shanghai Institute of Precision Medicine, Shanghai Ninth People’s Hospital, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaTranslational Medical Center for Stem Cell Therapy and Institute for Regenerative Medicine, Shanghai East Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai, ChinaTranslational Medical Center for Stem Cell Therapy and Institute for Regenerative Medicine, Shanghai East Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai, ChinaDepartment of Plastic and Reconstructive Surgery, Shanghai Institute of Precision Medicine, Shanghai Ninth People’s Hospital, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Thyroid and Breast Surgery, ZiBo Central Hospital Affiliated of Binzhou Medical University, Zibo, ChinaDepartment of Plastic and Reconstructive Surgery, Shanghai Institute of Precision Medicine, Shanghai Ninth People’s Hospital, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaThe melanocortin receptors are defined as a series of vital pharmaceutical targets to regulate neuronal appetite and maintain controllable body weight for mammals and teleosts. Melanocortin receptor accessory protein 2 (MRAP2) functions as an essential accessory player that modulates the surface translocation and binding to a variety of endogenous or synthetic hormones of central melanocortin-4 receptor (MC4R) signaling. MRAP2 is a single-transmembrane protein and could form a functional symmetric antiparallel homodimer topology. Here, we inverted the N-terminal, transmembrane, and C-terminal domains and generated six distinct conformational variants of the mouse MRAP2 to explore the functional orientations and the internal symmetry of MRAP2 dimers. These remolded MRAP2 mutants showed proper assembly of the antiparallel homodimer and binding to the MC4R, but slightly altered the regulatory profile on the surface expression and the ligand-stimulated cAMP cascades of MC4R. This study elucidated the importance of the orientation of each domain of the single-transmembrane protein and revealed the pharmacological properties of the internal symmetry of the antiparallel homodimer for MRAP2.https://www.frontiersin.org/articles/10.3389/fendo.2021.750797/fullMRAP2GPCRdimerizationinternal symmetryMC4R |
| spellingShingle | Meng Wang Linyu Pi Xiaowei Lei Lei Li Jing Xu Zhe Kuang Cong Zhang Liang Li Chao Zhang Functional Characterization of the Internal Symmetry of MRAP2 Antiparallel Homodimer Frontiers in Endocrinology MRAP2 GPCR dimerization internal symmetry MC4R |
| title | Functional Characterization of the Internal Symmetry of MRAP2 Antiparallel Homodimer |
| title_full | Functional Characterization of the Internal Symmetry of MRAP2 Antiparallel Homodimer |
| title_fullStr | Functional Characterization of the Internal Symmetry of MRAP2 Antiparallel Homodimer |
| title_full_unstemmed | Functional Characterization of the Internal Symmetry of MRAP2 Antiparallel Homodimer |
| title_short | Functional Characterization of the Internal Symmetry of MRAP2 Antiparallel Homodimer |
| title_sort | functional characterization of the internal symmetry of mrap2 antiparallel homodimer |
| topic | MRAP2 GPCR dimerization internal symmetry MC4R |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2021.750797/full |
| work_keys_str_mv | AT mengwang functionalcharacterizationoftheinternalsymmetryofmrap2antiparallelhomodimer AT linyupi functionalcharacterizationoftheinternalsymmetryofmrap2antiparallelhomodimer AT xiaoweilei functionalcharacterizationoftheinternalsymmetryofmrap2antiparallelhomodimer AT leili functionalcharacterizationoftheinternalsymmetryofmrap2antiparallelhomodimer AT jingxu functionalcharacterizationoftheinternalsymmetryofmrap2antiparallelhomodimer AT zhekuang functionalcharacterizationoftheinternalsymmetryofmrap2antiparallelhomodimer AT congzhang functionalcharacterizationoftheinternalsymmetryofmrap2antiparallelhomodimer AT liangli functionalcharacterizationoftheinternalsymmetryofmrap2antiparallelhomodimer AT chaozhang functionalcharacterizationoftheinternalsymmetryofmrap2antiparallelhomodimer |