Membrane orientation and oligomerization of the melanocortin receptor accessory protein 2.
- Resource Type
- Article
- Authors
- Chen, Valerie; Bruno, Antonio E.; Britt, Laura L.; Hernandez, Ciria C.; Gimenez, Luis E.; Peisley, Alys; Cone, Roger D.; Millhauser, Glenn L.
- Source
- Journal of Biological Chemistry. 11/27/2020, Vol. 295 Issue 48, p16370-S-4. 14p.
- Subject
- *MELANOCORTIN receptors
*PROTEIN receptors
*OLIGOMERIZATION
*INGESTION
*DIMERIZATION
*G protein coupled receptors
- Language
- ISSN
- 0021-9258
The melanocortin receptor accessory protein 2 (MRAP2) plays a pivotal role in the regulation of several G protein- coupled receptors that are essential for energy balance and food intake. MRAP2 loss-of-function results in obesity in mammals. MRAP2 and its homologMRAP1 have an unusualmembrane topology and are the only known eukaryotic proteins that thread into themembrane in both orientations. In this study, we demonstrate that the conserved polybasic motif that dictates the membrane topology and dimerization of MRAP1 does not control the membrane orientation and dimerization of MRAP2. We also show that MRAP2 dimerizes through its transmembrane domain and can form higher-order oligomers that arrangeMRAP2monomers in a parallel orientation. Investigating the molecular details ofMRAP2 structure is essential for understanding themechanism by which it regulates G protein-coupled receptors and will aid in elucidating the pathways involved inmetabolic dysfunction. [ABSTRACT FROM AUTHOR]