Structural insights on melanocortin 5 receptor targeting to cell surface

Abstract

The melanocortin 5 receptor (MC5R) is a G-protein coupled receptor (GPCR) with a typical seventransmembrane-domain structure. It is assumed that all GPCRs undergo several post-transcriptional modifications during synthesis and folding until finally target to the cell membrane. The available information about the specific domains responsible for the correct targeting of the melanocortin receptors to the cell surface is scarce. Regarding MC5R, it was shown that the first 20 aminoacids of the human receptor can be deleted without affecting the ligand binding affinity, but further deletions of the N terminus resulted in total loss of binding. These results were not directly correlated with the cell surface expression levels of the receptor. Thus, we aim to define the specific MC5R domains important to its correct trafficking and signaling, and preliminary results are here presented.