EMDB/PDB/SASBDBから引用されている文献のデータベース

キーワード
構造解析手法	All X線回折 NMR 電子顕微鏡小角散乱中性子線回折線維回折粉末回折赤外分光 EPR FRET 理論モデルハイブリッド
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

タイトル	Structure, function and pharmacology of human itch receptor complexes.
ジャーナル・号・ページ	Nature, Vol. 600, Issue 7887, Page 164-169, Year 2021
掲載日	2021年11月17日
著者	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 要旨	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.
リンク	Nature / PubMed:34789875
手法	EM (単粒子)
解像度	2.76 - 3.5 Å
構造データ	31918 7vdh EMDB-31918, PDB-7vdh: Cryo-EM structure of pseudoallergen receptor MRGPRX2 complex with C48/80, state2 手法: EM (単粒子) / 解像度: 2.9 Å 31922 7vdl EMDB-31922, PDB-7vdl: Cryo-EM structure of pseudoallergen receptor MRGPRX2 complex with circular cortistatin-14 手法: EM (単粒子) / 解像度: 3.22 Å 31923 7vdm EMDB-31923, PDB-7vdm: Cryo-EM structure of pseudoallergen receptor MRGPRX2 complex with substance P 手法: EM (単粒子) / 解像度: 2.98 Å 32131 7vuy EMDB-32131, PDB-7vuy: Cryo-EM structure of pseudoallergen receptor MRGPRX2 complex with PAMP-12. state1 手法: EM (単粒子) / 解像度: 2.84 Å 32132 7vuz EMDB-32132, PDB-7vuz: Cryo-EM structure of pseudoallergen receptor MRGPRX2 complex with PAMP-12, state2 手法: EM (単粒子) / 解像度: 2.89 Å 32133 7vv0 EMDB-32133, PDB-7vv0: Cryo-EM structure of pseudoallergen receptor MRGPRX2 complex with PAMP-12, local 手法: EM (単粒子) / 解像度: 3.5 Å 32136 7vv3 EMDB-32136, PDB-7vv3: Cryo-EM structure of pseudoallergen receptor MRGPRX2 complex with linear cortistatin-14 手法: EM (単粒子) / 解像度: 2.97 Å 32137 7vv4 EMDB-32137, PDB-7vv4: Cryo-EM structure of pseudoallergen receptor MRGPRX2 complex with linear cortistatin-14, local 手法: EM (単粒子) / 解像度: 2.97 Å 32138 7vv5 EMDB-32138, PDB-7vv5: Cryo-EM structure of pseudoallergen receptor MRGPRX2 complex with C48/80, state1 手法: EM (単粒子) / 解像度: 2.76 Å 32139 7vv6 EMDB-32139, PDB-7vv6: Cryo-EM structure of pseudoallergen receptor MRGPRX2 complex with C48/80 (local) 手法: EM (単粒子) / 解像度: 3.3 Å
化合物	ChemComp-CLR: CHOLESTEROL / コレステロ-ル 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 / 2,2′-[2-メトキシ-5-[2-(メチルアミノ)エチル]-1,3-フェニレンビス[メチレン(4-メトキシ-3,1-(以下略)
由来	homo sapiens (ヒト)
キーワード	MEMBRANE PROTEIN / G Protein-Coupled Receptor