View source for 8iod


==Cryo-EM structure of the PG-901-bound human melanocortin receptor 5 (MC5R)-Gs complex==
<StructureSection load='8iod' size='340' side='right'caption='[[8iod]], [[Resolution|resolution]] 2.59&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8iod]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Bos_taurus Bos taurus], [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens], [https://en.wikipedia.org/wiki/Influenza_A_virus_(A/Victoria/3/1975(H3N2)) Influenza A virus (A/Victoria/3/1975(H3N2))] 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=8IOD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8IOD 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]] 2.59&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4J2:(2R)-2-AMINO-3-(NAPHTHALEN-2-YL)PROPANOIC+ACID'>4J2</scene>, <scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=NH2:AMINO+GROUP'>NH2</scene>, <scene name='pdbligand=NLE:NORLEUCINE'>NLE</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=8iod FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8iod OCA], [https://pdbe.org/8iod PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8iod RCSB], [https://www.ebi.ac.uk/pdbsum/8iod PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8iod ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/GBG2_BOVIN GBG2_BOVIN] 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.
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== Publication Abstract from PubMed ==
Members of the melanocortin receptor (MCR) family that recognize different melanocortin peptides mediate a broad spectrum of cellular processes including energy homeostasis, inflammation and skin pigmentation through five MCR subtypes (MC1R-MC5R). The structural basis of subtype selectivity of the endogenous agonist gamma-MSH and non-selectivity of agonist alpha-MSH remains elusive, as the two agonists are highly similar with a conserved HFRW motif. Here, we report three cryo-electron microscopy structures of MC3R-G(s) in complex with gamma-MSH and MC5R-G(s) in the presence of alpha-MSH or a potent synthetic agonist PG-901. The structures reveal that alpha-MSH and gamma-MSH adopt a "U-shape" conformation, penetrate into the wide-open orthosteric pocket and form massive common contacts with MCRs via the HFRW motif. The C-terminus of gamma-MSH occupies an MC3R-specific complementary binding groove likely conferring subtype selectivity, whereas that of alpha-MSH distances itself from the receptor with neglectable contacts. PG-901 achieves the same potency as alpha-MSH with a shorter length by rebalancing the recognition site and mimicking the intra-peptide salt bridge in alpha-MSH by cyclization. Solid density confirmed the calcium ion binding in MC3R and MC5R, and the distinct modulation effects of divalent ions were demonstrated. Our results provide insights into ligand recognition and subtype selectivity among MCRs, and expand the knowledge of signal transduction among MCR family members.

Structural insights into ligand recognition and subtype selectivity of the human melanocortin-3 and melanocortin-5 receptors.,Feng W, Zhou Q, Chen X, Dai A, Cai X, Liu X, Zhao F, Chen Y, Ye C, Xu Y, Cong Z, Li H, Lin S, Yang D, Wang MW Cell Discov. 2023 Jul 31;9(1):81. doi: 10.1038/s41421-023-00586-4. PMID:37524700<ref>PMID:37524700</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8iod" style="background-color:#fffaf0;"></div>

==See Also==
*[[Transducin 3D structures|Transducin 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Bos taurus]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Synthetic construct]]
[[Category: Cai XQ]]
[[Category: Chen XY]]
[[Category: Chen Y]]
[[Category: Cong ZT]]
[[Category: Dai AT]]
[[Category: Feng WB]]
[[Category: Li H]]
[[Category: Lin S]]
[[Category: Liu X]]
[[Category: Wang MW]]
[[Category: Xu YN]]
[[Category: Yang DH]]
[[Category: Ye CY]]
[[Category: Zhao FH]]
[[Category: Zhou QT]]