Journal: Science / Year: 2021 Title: Structure reveals the activation mechanism of the MC4 receptor to initiate satiation signaling. Authors: Hadar Israeli / Oksana Degtjarik / Fabrizio Fierro / Vidicha Chunilal / Amandeep Kaur Gill / Nicolas J Roth / Joaquin Botta / Vadivel Prabahar / Yoav Peleg / Li F Chan / Danny Ben-Zvi / ...Authors: Hadar Israeli / Oksana Degtjarik / Fabrizio Fierro / Vidicha Chunilal / Amandeep Kaur Gill / Nicolas J Roth / Joaquin Botta / Vadivel Prabahar / Yoav Peleg / Li F Chan / Danny Ben-Zvi / Peter J McCormick / Masha Y Niv / Moran Shalev-Benami / Abstract: Obesity is a global epidemic that causes 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 ...Obesity is a global epidemic that causes 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-electron microscopy (cryo-EM) structure of the human MC4R-G 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 calcium (Ca) is required for agonist, but not antagonist, efficacy. These results fill a gap in the understanding of MC4R activation and could guide the design of future weight-management drugs.
History
Deposition
Nov 2, 2020
-
Header (metadata) release
Apr 28, 2021
-
Map release
Apr 28, 2021
-
Update
Mar 15, 2023
-
Current status
Mar 15, 2023
Processing site: PDBe / Status: Released
-
Structure visualization
Movie
Surface view with section colored by density value
In the structure databanks used in Yorodumi, some data are registered as the other names, "COVID-19 virus" and "2019-nCoV". Here are the details of the virus and the list of structure data.
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)
EMDB accession codes are about to change! (news from PDBe EMDB page)
The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
The EM Navigator/Yorodumi systems omit the EMD- prefix.
Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator
Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.
Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi