![[feed]](/style/images/feed-icon-14x14.png){kind=icon}
Tools
Tools
Preview |
PDF (Original Article)
- Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
4MB |
![[thumbnail of Supplementary Information]](https://edoc.mdc-berlin.de/style/images/fileicons/other.png) |
Other (Supplementary Information)
9MB |
| Item Type: | Article |
|---|---|
| Title: | MRAP2 modifies the signaling and oligomerization state of the melanocortin-4 receptor |
| Creators: |
Sohail, Iqra  ORCID: https://orcid.org/0009-0007-1828-4098, Laurin, Suli-Anne, Kleinau, Gunnar, Chunilal, Vidicha, Morton, Andrew, Brenlla, Alfonso, Uretmen Kagiali, Zeynep Cansu ORCID: https://orcid.org/0000-0003-0007-5814, Blouin, Marie-José ORCID: https://orcid.org/0009-0003-8032-2789, Tello, Javier A. ORCID: https://orcid.org/0000-0001-6637-2155, Beck-Sickinger, Annette G. ORCID: https://orcid.org/0000-0003-4560-8020, Lohse, Martin J. ORCID: https://orcid.org/0000-0002-0599-3510, Scheerer, Patrick ORCID: https://orcid.org/0000-0001-5028-2075, Bouvier, Michel ORCID: https://orcid.org/0000-0003-1128-0100, McCormick, Peter ORCID: https://orcid.org/0000-0002-2225-5181, Annibale, Paolo ORCID: https://orcid.org/0000-0003-3208-5347 and Biebermann, Heike ORCID: https://orcid.org/0000-0002-2024-7778
|
| Abstract: | The melanocortin-4 receptor is a G protein-coupled receptor and a key regulator of appetite and metabolism. It can interact with the melanocortin-receptor accessory protein 2, a single transmembrane helix protein known to interact with several different G protein-coupled receptors. However, the consequences of this interaction are not completely understood. Here we report that co-expression of melanocortin-receptor accessory protein 2 has multiple effects on the melanocortin-4 receptor: it enhances G protein-mediated signaling and simultaneously impairs β-arrestin2 recruitment and, consequently, internalization. In addition, co-expression of melanocortin-receptor accessory protein 2 leads to an increased number of monomers of melanocortin-4 receptor by disrupting receptor oligomers. A structural homology model of the active state melanocortin-4 receptor – melanocortin-receptor accessory protein 2 – Gαs complex suggests interaction sites that are relevant for receptor activation. Our data indicate that melanocortin-receptor accessory protein 2 is an accessory protein that interacts with and influences melanocortin-4 receptor structure, biasing its signaling towards G protein-mediated effects. |
| Keywords: | Beta-Arrestin 2, HEK293 Cells, Membrane Proteins, Molecular Models, Protein Binding, Protein Multimerization, Signal Transducing Adaptor Proteins, Signal Transduction, Type 4 Melanocortin Receptor, Animals |
| Source: | Nature Communications |
| ISSN: | 2041-1723 |
| Publisher: | Nature Publishing Group |
| Volume: | 16 |
| Number: | 1 |
| Page Range: | 8324 |
| Date: | 25 September 2025 |
| Official Publication: | https://doi.org/10.1038/s41467-025-63988-w |
| PubMed: | View item in PubMed |
| Related to: |
Repository Staff Only: item control page
