The ‘Hunger Games’- Structural Studies of the MC4 Receptor Reveal Mechanism for Satiety
Host: Sagi Levy
Abstract: Obesity is aglobal epidemic causing increased morbidity and impaired quality of life. Themelanocortin 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 foranti-obesity drugs. MC4R is a member of the GPCR superfamily and signalsprimarily through the heterotrimeric G protein Gs. Throughcombination of structural-, biochemical- and cellular- studies we determinedthe cryo-EM structure of the human MC4R-Gs signaling complex, andexplored the cellular conduits for signal transduction in health and disease.The work reveals the mechanism of MC4R activation, highlighting a molecularswitch that signals satiation. These results fill a major gap in understandingMC4R activation and guide the design of future weight management drugs.
