dc.contributor.author | Israeli, H | |
dc.contributor.author | Degtjarik, O | |
dc.contributor.author | Fierro, F | |
dc.contributor.author | Chunilal, V | |
dc.contributor.author | Gill, AK | |
dc.contributor.author | Roth, NJ | |
dc.contributor.author | Botta, J | |
dc.contributor.author | Prabahar, V | |
dc.contributor.author | Peleg, Y | |
dc.contributor.author | Chan, LF | |
dc.contributor.author | Ben-Zvi, D | |
dc.contributor.author | McCormick, PJ | |
dc.contributor.author | Niv, MY | |
dc.contributor.author | Shalev-Benami, M | |
dc.date.accessioned | 2021-04-27T08:43:46Z | |
dc.date.available | 2021-04-27T08:43:46Z | |
dc.identifier.issn | 0036-8075 | |
dc.identifier.uri | https://qmro.qmul.ac.uk/xmlui/handle/123456789/71518 | |
dc.description.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. | en_US |
dc.format.extent | eabf7958 - eabf7958 | |
dc.language | en | |
dc.publisher | American Association for the Advancement of Science (AAAS) | en_US |
dc.relation.ispartof | Science | |
dc.rights | “This is the author’s version of the work. It is posted here by permission of the AAAS for personal use, not for redistribution. The definitive version was published in Science 15 Apr 2021: eabf7958 DOI: 10.1126/science.abf7958” | |
dc.title | Structure reveals the activation mechanism of the MC4 receptor to initiate satiation signaling | en_US |
dc.type | Article | en_US |
dc.identifier.doi | 10.1126/science.abf7958 | |
pubs.notes | Not known | en_US |
pubs.publication-status | Published online | en_US |
pubs.publisher-url | https://doi.org/10.1126/science.abf7958 | |
rioxxterms.funder | Default funder | en_US |
rioxxterms.identifier.project | Default project | en_US |