View source for 7vdm


==Cryo-EM structure of pseudoallergen receptor MRGPRX2 complex with substance P==
<StructureSection load='7vdm' size='340' side='right'caption='[[7vdm]], [[Resolution|resolution]] 2.98&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7vdm]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7VDM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7VDM 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]] 2.98&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CLR:CHOLESTEROL'>CLR</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=7vdm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7vdm OCA], [https://pdbe.org/7vdm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7vdm RCSB], [https://www.ebi.ac.uk/pdbsum/7vdm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7vdm 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).
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== Publication Abstract from PubMed ==
In the clades of animals that diverged from the bony fish, a group of Mas-related G-protein-coupled receptors (MRGPRs) evolved that have an active role in itch and allergic signals(1,2). As an MRGPR, MRGPRX2 is known to sense basic secretagogues (agents that promote secretion) and is involved in itch signals and eliciting pseudoallergic reactions(3-6). MRGPRX2 has been targeted by drug development efforts to prevent the side effects induced by certain drugs or to treat allergic diseases. Here we report a set of cryo-electron microscopy structures of the MRGPRX2-Gi1 trimer in complex with polycationic compound 48/80 or with inflammatory peptides. The structures of the MRGPRX2-Gi1 complex exhibited shallow, solvent-exposed ligand-binding pockets. We identified key common structural features of MRGPRX2 and describe a consensus motif for peptidic allergens. Beneath the ligand-binding pocket, the unusual kink formation at transmembrane domain 6 (TM6) and the replacement of the general toggle switch from Trp(6.48) to Gly(6.48) (superscript annotations as per Ballesteros-Weinstein nomenclature) suggest a distinct activation process. We characterized the interfaces of MRGPRX2 and the Gi trimer, and mapped the residues associated with key single-nucleotide polymorphisms on both the ligand and G-protein interfaces of MRGPRX2. Collectively, our results provide a structural basis for the sensing of cationic allergens by MRGPRX2, potentially facilitating the rational design of therapies to prevent unwanted pseudoallergic reactions.

Structure, function and pharmacology of human itch receptor complexes.,Yang F, Guo L, Li Y, Wang G, Wang J, Zhang C, Fang GX, Chen X, Liu L, Yan X, Liu Q, Qu C, Xu Y, Xiao P, Zhu Z, Li Z, Zhou J, Yu X, Gao N, Sun JP Nature. 2021 Dec;600(7887):164-169. doi: 10.1038/s41586-021-04077-y. Epub 2021, Nov 17. PMID:34789875<ref>PMID:34789875</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 7vdm" style="background-color:#fffaf0;"></div>

==See Also==
*[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]]
*[[Transducin 3D structures|Transducin 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Li Y]]
[[Category: Yang F]]