Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Structure, function and pharmacology of human itch receptor complexes.
Journal, issue, pages	Nature, Vol. 600, Issue 7887, Page 164-169, Year 2021
Publish date	Nov 17, 2021
Authors	Fan Yang / Lulu Guo / Yu Li / Guopeng Wang / Jia Wang / Chao Zhang / Guo-Xing Fang / Xu Chen / Lei Liu / Xu Yan / Qun Liu / Changxiu Qu / Yunfei Xu / Peng Xiao / Zhongliang Zhu / Zijian Li / Jiuyao Zhou / Xiao Yu / Ning Gao / Jin-Peng Sun /
PubMed Abstract	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. As an MRGPR, ...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. As an MRGPR, MRGPRX2 is known to sense basic secretagogues (agents that promote secretion) and is involved in itch signals and eliciting pseudoallergic reactions. 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-G trimer in complex with polycationic compound 48/80 or with inflammatory peptides. The structures of the MRGPRX2-G 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 to Gly (superscript annotations as per Ballesteros-Weinstein nomenclature) suggest a distinct activation process. We characterized the interfaces of MRGPRX2 and the G 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.
External links	Nature / PubMed:34789875
Methods	EM (single particle)
Resolution	2.76 - 3.5 Å
Structure data	31918 7vdh EMDB-31918, PDB-7vdh: Cryo-EM structure of pseudoallergen receptor MRGPRX2 complex with C48/80, state2 Method: EM (single particle) / Resolution: 2.9 Å 31922 7vdl EMDB-31922, PDB-7vdl: Cryo-EM structure of pseudoallergen receptor MRGPRX2 complex with circular cortistatin-14 Method: EM (single particle) / Resolution: 3.22 Å 31923 7vdm EMDB-31923, PDB-7vdm: Cryo-EM structure of pseudoallergen receptor MRGPRX2 complex with substance P Method: EM (single particle) / Resolution: 2.98 Å 32131 7vuy EMDB-32131, PDB-7vuy: Cryo-EM structure of pseudoallergen receptor MRGPRX2 complex with PAMP-12. state1 Method: EM (single particle) / Resolution: 2.84 Å 32132 7vuz EMDB-32132, PDB-7vuz: Cryo-EM structure of pseudoallergen receptor MRGPRX2 complex with PAMP-12, state2 Method: EM (single particle) / Resolution: 2.89 Å 32133 7vv0 EMDB-32133, PDB-7vv0: Cryo-EM structure of pseudoallergen receptor MRGPRX2 complex with PAMP-12, local Method: EM (single particle) / Resolution: 3.5 Å 32136 7vv3 EMDB-32136, PDB-7vv3: Cryo-EM structure of pseudoallergen receptor MRGPRX2 complex with linear cortistatin-14 Method: EM (single particle) / Resolution: 2.97 Å 32137 7vv4 EMDB-32137, PDB-7vv4: Cryo-EM structure of pseudoallergen receptor MRGPRX2 complex with linear cortistatin-14, local Method: EM (single particle) / Resolution: 2.97 Å 32138 7vv5 EMDB-32138, PDB-7vv5: Cryo-EM structure of pseudoallergen receptor MRGPRX2 complex with C48/80, state1 Method: EM (single particle) / Resolution: 2.76 Å 32139 7vv6 EMDB-32139, PDB-7vv6: Cryo-EM structure of pseudoallergen receptor MRGPRX2 complex with C48/80 (local) Method: EM (single particle) / Resolution: 3.3 Å
Chemicals	ChemComp-CLR: CHOLESTEROL / Cholesterol ChemComp-6IB: 2-[4-methoxy-3-[[2-methoxy-3-[[2-methoxy-5-[2-(methylamino)ethyl]phenyl]methyl]-5-[2-(methylamino)ethyl]phenyl]methyl]phenyl]-~{N}-methyl-ethanamine
Source	homo sapiens (human)
Keywords	MEMBRANE PROTEIN / G Protein-Coupled Receptor