View source for 7f4d


==Cryo-EM structure of alpha-MSH-bound melanocortin-1 receptor in complex with Gs protein and Nb35==
<StructureSection load='7f4d' size='340' side='right'caption='[[7f4d]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7f4d]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] 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=7F4D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7F4D FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</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=7f4d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7f4d OCA], [https://pdbe.org/7f4d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7f4d RCSB], [https://www.ebi.ac.uk/pdbsum/7f4d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7f4d ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/GBG2_HUMAN GBG2_HUMAN] Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein-effector interaction (By similarity).
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Melanocortins are peptide hormones critical for the regulation of stress response, energy homeostasis, inflammation, and skin pigmentation. Their functions are mediated by five G protein-coupled receptors (MC1R-MC5R), predominately through the stimulatory G protein (Gs). MC1R, the founding member of melanocortin receptors, is mainly expressed in melanocytes and is involved in melanogenesis. Dysfunction of MC1R is associated with the development of melanoma and skin cancer. Here we present three cryo-electron microscopy structures of the MC1R-Gs complexes bound to endogenous hormone alpha-MSH, a marketed drug afamelanotide, and a synthetic agonist SHU9119. These structures reveal the orthosteric binding pocket for the conserved HFRW motif among melanocortins and the crucial role of calcium ion in ligand binding. They also demonstrate the basis of differential activities among different ligands. In addition, unexpected interactions between MC1R and the Gbeta subunit were discovered from these structures. Together, our results elucidate a conserved mechanism of calcium-mediated ligand recognition, a specific mode of G protein coupling, and a universal activation pathway of melanocortin receptors.

Structural mechanism of calcium-mediated hormone recognition and Gbeta interaction by the human melanocortin-1 receptor.,Ma S, Chen Y, Dai A, Yin W, Guo J, Yang D, Zhou F, Jiang Y, Wang MW, Xu HE Cell Res. 2021 Oct;31(10):1061-1071. doi: 10.1038/s41422-021-00557-y. Epub 2021 , Aug 27. PMID:34453129<ref>PMID:34453129</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7f4d" style="background-color:#fffaf0;"></div>

==See Also==
*[[Transducin 3D structures|Transducin 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Synthetic construct]]
[[Category: Chen Y]]
[[Category: Dai A]]
[[Category: Guo J]]
[[Category: Jiang Y]]
[[Category: Ma S]]
[[Category: Wang M-W]]
[[Category: Xu HE]]
[[Category: Yang D]]
[[Category: Yin W]]
[[Category: Zhou F]]