Publications by year

<embed>

Publications by Authors

Recent Publications

More<embed>

Contact Us

Head of Institute: Prof. Oren Tirosh

Administrative manager: Ms. Yael Fruchter

Office Address:
Institute of Biochemistry, Food Science and Nutrition,
Robert H. Smith Faculty of Agriculture, Food and Environment,
The Hebrew University of Jerusalem, 
P.O.Box 12, Rehovot 7610001, ISRAEL

Tel: +972 - (0)8-9489385
Fax: +972 - (0)8-9363208
Email Address: yaelf@savion.huji.ac.il

Structure reveals the activation mechanism of the MC4 receptor to initiate satiation signaling

Citation:

Israeli, H. ; Degtjarik, O. ; Fierro, F. ; Chunilal, V. ; Gill, A. K. ; Roth, N. J. ; Botta, J. ; Prabahar, V. ; Peleg, Y. ; Chan, L. F. ; et al. Structure reveals the activation mechanism of the MC4 receptor to initiate satiation signaling. Science 2021, eabf7958.

Date Published:

2021/04/15

Abstract:

Obesity is a global epidemic causing morbidity and impaired quality of life. The melanocortin receptor 4 (MC4R) is at the crux of appetite, energy homeostasis, and body-weight control in the central nervous system and is a prime target for anti-obesity drugs. Here, we present the cryo-EM structure of the human MC4R-Gs signaling complex bound to the agonist setmelanotide, a cyclic peptide recently approved for the treatment of obesity. The work reveals the mechanism of MC4R activation, highlighting a molecular switch that initiates satiation signaling. In addition, our findings indicate that Ca2+ is required for agonist but not antagonist efficacy. These results fill a gap in understanding MC4R activation and could guide the design of future weight management drugs.

Website