View source for 7aue


==Melanocortin receptor 4 (MC4R) Gs protein complex==
<StructureSection load='7aue' size='340' side='right'caption='[[7aue]], [[Resolution|resolution]] 2.97&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7aue]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens], [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7AUE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AUE FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CY3:2-AMINO-3-MERCAPTO-PROPIONAMIDE'>CY3</scene>, <scene name='pdbligand=DAL:D-ALANINE'>DAL</scene>, <scene name='pdbligand=DPN:D-PHENYLALANINE'>DPN</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7aue FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7aue OCA], [https://pdbe.org/7aue PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7aue RCSB], [https://www.ebi.ac.uk/pdbsum/7aue PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7aue ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/MC4R_HUMAN MC4R_HUMAN] Obesity due to melanocortin 4 receptor deficiency. The disease is caused by mutations affecting the gene represented in this entry.
== Function ==
[https://www.uniprot.org/uniprot/MC4R_HUMAN MC4R_HUMAN] Receptor specific to the heptapeptide core common to adrenocorticotropic hormone and alpha-, beta-, and gamma-MSH. Plays a central role in energy homeostasis and somatic growth. This receptor is mediated by G proteins that stimulate adenylate cyclase (cAMP).<ref>PMID:12646665</ref> <ref>PMID:25163632</ref> 
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== Publication Abstract from PubMed ==
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(s) 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(2+)) 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.

Structure reveals the activation mechanism of the MC4 receptor to initiate satiation signaling.,Israeli H, Degtjarik O, Fierro F, Chunilal V, Gill AK, Roth NJ, Botta J, Prabahar V, Peleg Y, Chan LF, Ben-Zvi D, McCormick PJ, Niv MY, Shalev-Benami M Science. 2021 May 21;372(6544):808-814. doi: 10.1126/science.abf7958. Epub 2021 , Apr 15. PMID:33858992<ref>PMID:33858992</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 7aue" style="background-color:#fffaf0;"></div>

==See Also==
*[[Alice Clark/BRCT|Alice Clark/BRCT]]
*[[Transducin 3D structures|Transducin 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Synthetic construct]]
[[Category: Degtjarik O]]
[[Category: Israeli H]]
[[Category: Prabahar V]]
[[Category: Shalev-Benami M]]