Cell Res: The molecular mechanism of melanocortin receptor 1 calcium ion-mediated hormone recognition

On August 27, 2021, Xu Huaqiang's group from Shanghai Institute of Materia Medica, Chinese Academy of Sciences, and Wang Mingwei's group, published a titled "Structural mechanism of calcium-mediated hormone recognition and Gβ interaction by the human melanocortin-1 receptor" in Cell Research .

Melanocortin is an endogenous polypeptide hormone composed of adrenocorticotropic hormone (ACTH) and three melanocyte-stimulating hormones (α-MSH, β-MSH, and γ-MSH).

In view of the important role of the melanocortin system in the body, a variety of melanocortin polypeptide analogs have been developed as potential drugs for the treatment of skin diseases, obesity, anorexia and type 2 diabetes

However, due to the lack of understanding of the structure of melanocortin and its receptor complex, the specific mechanism of the interaction between melanocortin and the five melanocortin receptors is still unclear

In this study, the researchers analyzed the cryo-EM structure of MC1R coupled to Gs protein complex under different ligand stimulation (α-MSH, Afamelanotide and SHU9119), with resolutions of 3.

Also, in Afamelanotide? MC1R? In the three-dimensional reconstruction of the Gs complex, the researchers classified a complex conformation without the density of the Nb35 antibody

Figure 1.

This study provides a structural model for understanding the molecular mechanism of ligand recognition in the melanocortin system, and also provides a new idea for the design of drugs targeting the melanocortin receptor

The cryo-electron microscopy data for this work was collected on the cryo-electron microscopy platform of the Shanghai Institute of Materia Medica, Chinese Academy of Sciences

　　Full text link: https://　　(Contribution department: Xu Huaqiang's research group/Wang Mingwei's research group)