Membrane orientation and oligomerization of the melanocortin receptor accessory protein 2
- Resource Type
- Authors
- Chen, Valerie; Bruno, Antonio E; Britt, Laura L; Hernandez, Ciria C; Gimenez, Luis E; Peisley, Alys; Cone, Roger D; Millhauser, Glenn L
- Source
- The Journal of biological chemistry, vol 295, iss 48
- Subject
- obesity
Biochemistry & Molecular Biology
accessory protein
1.1 Normal biological development and functioning
Cell Membrane
Signal Transducing
Adaptor Proteins
transmembrane domain
coupled receptor
melanocortin receptor
Biological Sciences
Medical and Health Sciences
HEK293 Cells
Protein Domains
G protein–
G protein–coupled receptor
membrane threading
Underpinning research
Chemical Sciences
Humans
membrane protein
metabolic regulation
Protein Multimerization
- Language
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 homolog MRAP1 have an unusual membrane topology and are the only known eukaryotic proteins that thread into the membrane 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 arrange MRAP2 monomers in a parallel orientation. Investigating the molecular details of MRAP2 structure is essential for understanding the mechanism by which it regulates G protein-coupled receptors and will aid in elucidating the pathways involved in metabolic dysfunction.