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基本情報
登録情報 | データベース: EMDB / ID: EMD-32133 | |||||||||
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タイトル | Cryo-EM structure of pseudoallergen receptor MRGPRX2 complex with PAMP-12, local | |||||||||
![]() | Cryo-EM structure of pseudoallergen receptor MRGPRX2 complex with PAMP-12, local | |||||||||
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機能・相同性 | ![]() adrenomedullin receptor binding / positive regulation of progesterone biosynthetic process / mast cell secretagogue receptor activity / vascular associated smooth muscle cell development / neuron projection regeneration / adrenomedullin receptor signaling pathway / mast cell activation / spongiotrophoblast layer development / Calcitonin-like ligand receptors / branching involved in labyrinthine layer morphogenesis ...adrenomedullin receptor binding / positive regulation of progesterone biosynthetic process / mast cell secretagogue receptor activity / vascular associated smooth muscle cell development / neuron projection regeneration / adrenomedullin receptor signaling pathway / mast cell activation / spongiotrophoblast layer development / Calcitonin-like ligand receptors / branching involved in labyrinthine layer morphogenesis / positive regulation of vasculogenesis / regulation of systemic arterial blood pressure / regulation of the force of heart contraction / sleep / neuropeptide binding / regulation of urine volume / G protein-coupled receptor internalization / negative regulation of vascular permeability / negative regulation of vasoconstriction / positive regulation of heart rate / mast cell degranulation / response to starvation / positive regulation of cytokinesis / odontogenesis of dentin-containing tooth / androgen metabolic process / developmental growth / vasculogenesis / animal organ regeneration / response to glucocorticoid / sensory perception of pain / cAMP-mediated signaling / neural tube closure / female pregnancy / G protein-coupled receptor activity / response to insulin / adenylate cyclase-activating G protein-coupled receptor signaling pathway / hormone activity / receptor internalization / positive regulation of angiogenesis / heart development / positive regulation of cytosolic calcium ion concentration / G alpha (s) signalling events / cell population proliferation / response to lipopolysaccharide / response to hypoxia / inflammatory response / positive regulation of apoptotic process / G protein-coupled receptor signaling pathway / negative regulation of cell population proliferation / signaling receptor binding / positive regulation of cell population proliferation / signal transduction / extracellular space / extracellular region / membrane / plasma membrane / cytoplasm 類似検索 - 分子機能 | |||||||||
生物種 | ![]() | |||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.5 Å | |||||||||
![]() | Li Y / Yang F | |||||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Structure, function and pharmacology of human itch receptor complexes. 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 / ...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 / ![]() 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. | |||||||||
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マップデータ | ![]() | 29.3 MB | ![]() | |
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画像 | ![]() | 25.6 KB | ||
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-関連構造データ
関連構造データ | ![]() 7vv0MC ![]() 7vdhC ![]() 7vdlC ![]() 7vdmC ![]() 7vuyC ![]() 7vuzC ![]() 7vv3C ![]() 7vv4C ![]() 7vv5C ![]() 7vv6C M: このマップから作成された原子モデル C: 同じ文献を引用 ( |
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注釈 | Cryo-EM structure of pseudoallergen receptor MRGPRX2 complex with PAMP-12, local | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 0.8286 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
CCP4マップ ヘッダ情報:
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試料の構成要素
-全体 : Cryo-EM structure of pseudoallergen receptor MRGPRX2 complex with...
全体 | 名称: Cryo-EM structure of pseudoallergen receptor MRGPRX2 complex with PAMP-12, local |
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要素 |
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-超分子 #1: Cryo-EM structure of pseudoallergen receptor MRGPRX2 complex with...
超分子 | 名称: Cryo-EM structure of pseudoallergen receptor MRGPRX2 complex with PAMP-12, local タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1-#2 |
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由来(天然) | 生物種: ![]() |
-分子 #1: peptide from Pro-adrenomedullin
分子 | 名称: peptide from Pro-adrenomedullin / タイプ: protein_or_peptide / ID: 1 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 1.624952 KDa |
配列 | 文字列: FRKKWNKWAL SR |
-分子 #2: Mas-related G-protein coupled receptor member X2
分子 | 名称: Mas-related G-protein coupled receptor member X2 / タイプ: protein_or_peptide / ID: 2 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 37.123984 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: MDPTTPAWGT ESTTVNGNDQ ALLLLCGKET LIPVFLILFI ALVGLVGNGF VLWLLGFRMR RNAFSVYVLS LAGADFLFLC FQIINCLVY LSNFFCSISI NFPSFFTTVM TCAYLAGLSM LSTVSTERCL SVLWPIWYRC RRPRHLSAVV CVLLWALSLL L SILEGKFC ...文字列: MDPTTPAWGT ESTTVNGNDQ ALLLLCGKET LIPVFLILFI ALVGLVGNGF VLWLLGFRMR RNAFSVYVLS LAGADFLFLC FQIINCLVY LSNFFCSISI NFPSFFTTVM TCAYLAGLSM LSTVSTERCL SVLWPIWYRC RRPRHLSAVV CVLLWALSLL L SILEGKFC GFLFSDGDSG WCQTFDFITA AWLIFLFMVL CGSSLALLVR ILCGSRGLPL TRLYLTILLT VLVFLLCGLP FG IQWFLIL WIWKDSDVLF CHIHPVSVVL SSLNSSANPI IYFFVGSFRK QWRLQQPILK LALQRALQDI AEVDHSEGCF RQG TPEMSR SSLV |
-分子 #3: CHOLESTEROL
分子 | 名称: CHOLESTEROL / タイプ: ligand / ID: 3 / コピー数: 1 / 式: CLR |
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分子量 | 理論値: 386.654 Da |
Chemical component information | ![]() ChemComp-CLR: |
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
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![]() | 単粒子再構成法 |
試料の集合状態 | particle |
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試料調製
緩衝液 | pH: 7.5 |
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凍結 | 凍結剤: ETHANE |
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電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
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撮影 | フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) 平均電子線量: 58.0 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: ![]() |
電子光学系 | 照射モード: SPOT SCAN / 撮影モード: BRIGHT FIELD |
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |
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画像解析
最終 再構成 | 解像度のタイプ: BY AUTHOR / 解像度: 3.5 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 978001 |
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初期 角度割当 | タイプ: ANGULAR RECONSTITUTION |
最終 角度割当 | タイプ: ANGULAR RECONSTITUTION |