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データを開く
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基本情報
| 登録情報 | ![]() | |||||||||
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| タイトル | CryoEM structure of Gi-coupled MRGPRX1 with peptide agonist BAM8-22 | |||||||||
マップデータ | ||||||||||
試料 |
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キーワード | itch receptor / Mas-related GPCRs / MRGPRX1 / STRUCTURAL PROTEIN | |||||||||
| 機能・相同性 | 機能・相同性情報synaptic vesicle lumen / response to chloroquine / chromaffin granule lumen / sneeze reflex / opioid peptide activity / opioid receptor binding / aggressive behavior / positive regulation of behavioral fear response / general adaptation syndrome, behavioral process / neuronal dense core vesicle lumen ...synaptic vesicle lumen / response to chloroquine / chromaffin granule lumen / sneeze reflex / opioid peptide activity / opioid receptor binding / aggressive behavior / positive regulation of behavioral fear response / general adaptation syndrome, behavioral process / neuronal dense core vesicle lumen / symmetric synapse / synaptic signaling via neuropeptide / response to epinephrine / sensory perception of itch / negative regulation of sensory perception of pain / cell body fiber / response to peptide / G protein-coupled opioid receptor signaling pathway / drinking behavior / cellular response to vitamin D / neuropeptide hormone activity / behavioral response to ethanol / sensory perception / response to immobilization stress / startle response / transmission of nerve impulse / locomotory exploration behavior / cellular response to transforming growth factor beta stimulus / glial cell proliferation / behavioral fear response / adenylate cyclase inhibitor activity / positive regulation of protein localization to cell cortex / T cell migration / positive regulation of relaxation of smooth muscle / Adenylate cyclase inhibitory pathway / D2 dopamine receptor binding / adenylate cyclase-inhibiting serotonin receptor signaling pathway / G protein-coupled serotonin receptor binding / sensory perception of pain / cellular response to forskolin / axon terminus / cellular response to cAMP / Peptide ligand-binding receptors / regulation of mitotic spindle organization / acute-phase response / chemokine-mediated signaling pathway / response to nicotine / Post-translational protein phosphorylation / Regulation of insulin secretion / neuropeptide signaling pathway / response to prostaglandin E / positive regulation of cholesterol biosynthetic process / cellular response to virus / negative regulation of insulin secretion / response to calcium ion / G protein-coupled receptor binding / response to peptide hormone / G protein-coupled receptor activity / response to toxic substance / Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / G-protein beta/gamma-subunit complex binding / centriolar satellite / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / Olfactory Signaling Pathway / Activation of the phototransduction cascade / G protein-coupled acetylcholine receptor signaling pathway / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / osteoblast differentiation / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / G-protein activation / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / photoreceptor disc membrane / ADP signalling through P2Y purinoceptor 12 / Sensory perception of sweet, bitter, and umami (glutamate) taste / GDP binding / Glucagon-type ligand receptors / Adrenaline,noradrenaline inhibits insulin secretion / response to estradiol / Vasopressin regulates renal water homeostasis via Aquaporins / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / transmembrane signaling receptor activity / G alpha (z) signalling events / cellular response to catecholamine stimulus / ADP signalling through P2Y purinoceptor 1 / ADORA2B mediated anti-inflammatory cytokines production / G beta:gamma signalling through PI3Kgamma / adenylate cyclase-activating dopamine receptor signaling pathway / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / GPER1 signaling / cellular response to prostaglandin E stimulus / heterotrimeric G-protein complex / G-protein beta-subunit binding 類似検索 - 分子機能 | |||||||||
| 生物種 | Homo sapiens (ヒト) | |||||||||
| 手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.0 Å | |||||||||
データ登録者 | Sun JP / Xu HE / Yang F / Liu ZM / Guo LL / Zhang YM / Fang GX / Tie L / Zhuang YM / Xue CY | |||||||||
| 資金援助 | 中国, 2件
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引用 | ジャーナル: Nat Commun / 年: 2023タイトル: Ligand recognition and G protein coupling of the human itch receptor MRGPRX1. 著者: Lulu Guo / Yumu Zhang / Guoxing Fang / Lu Tie / Yuming Zhuang / Chenyang Xue / Qi Liu / Minghui Zhang / Kongkai Zhu / Chongzhao You / Peiyu Xu / Qingning Yuan / Chao Zhang / Lei Liu / Naikang ...著者: Lulu Guo / Yumu Zhang / Guoxing Fang / Lu Tie / Yuming Zhuang / Chenyang Xue / Qi Liu / Minghui Zhang / Kongkai Zhu / Chongzhao You / Peiyu Xu / Qingning Yuan / Chao Zhang / Lei Liu / Naikang Rong / Shengxuan Peng / Yuan Liu / Chuanzheng Wang / Xin Luo / Zongyao Lv / Dongwei Kang / Xiao Yu / Cheng Zhang / Yi Jiang / Xinzhong Dong / Jiuyao Zhou / Zhongmin Liu / Fan Yang / H Eric Xu / Jin-Peng Sun / ![]() 要旨: MRGPRX1, a Mas-related GPCR (MRGPR), is a key receptor for itch perception and targeting MRGPRX1 may have potential to treat both chronic itch and pain. Here we report cryo-EM structures of the ...MRGPRX1, a Mas-related GPCR (MRGPR), is a key receptor for itch perception and targeting MRGPRX1 may have potential to treat both chronic itch and pain. Here we report cryo-EM structures of the MRGPRX1-Gi1 and MRGPRX1-Gq trimers in complex with two peptide ligands, BAM8-22 and CNF-Tx2. These structures reveal a shallow orthosteric pocket and its conformational plasticity for sensing multiple different peptidic itch allergens. Distinct from MRGPRX2, MRGPRX1 contains a unique pocket feature at the extracellular ends of TM3 and TM4 to accommodate the peptide C-terminal "RF/RY" motif, which could serve as key mechanisms for peptidic allergen recognition. Below the ligand binding pocket, the GXPFGXF/W motif is essential for the inward tilting of the upper end of TM6 to induce receptor activation. Moreover, structural features inside the ligand pocket and on the cytoplasmic side of MRGPRX1 are identified as key elements for both Gi and Gq signaling. Collectively, our studies provide structural insights into understanding itch sensation, MRGPRX1 activation, and downstream G protein signaling. | |||||||||
| 履歴 |
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構造の表示
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ダウンロードとリンク
-EMDBアーカイブ
| マップデータ | emd_36233.map.gz | 33 MB | EMDBマップデータ形式 | |
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| ヘッダ (付随情報) | emd-36233-v30.xml emd-36233.xml | 21 KB 21 KB | 表示 表示 | EMDBヘッダ |
| 画像 | emd_36233.png | 89.2 KB | ||
| Filedesc metadata | emd-36233.cif.gz | 6.6 KB | ||
| その他 | emd_36233_half_map_1.map.gz emd_36233_half_map_2.map.gz | 59.3 MB 59.3 MB | ||
| アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-36233 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-36233 | HTTPS FTP |
-関連構造データ
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リンク
| EMDBのページ | EMDB (EBI/PDBe) / EMDataResource |
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| 「今月の分子」の関連する項目 |
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マップ
| ファイル | ダウンロード / ファイル: emd_36233.map.gz / 形式: CCP4 / 大きさ: 64 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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| 投影像・断面図 | 画像のコントロール
画像は Spider により作成 | ||||||||||||||||||||||||||||||||||||
| ボクセルのサイズ | X=Y=Z: 0.89 Å | ||||||||||||||||||||||||||||||||||||
| 密度 |
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| 対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||
| 詳細 | EMDB XML:
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-添付データ
-ハーフマップ: #2
| ファイル | emd_36233_half_map_1.map | ||||||||||||
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| 投影像・断面図 |
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| 密度ヒストグラム |
-ハーフマップ: #1
| ファイル | emd_36233_half_map_2.map | ||||||||||||
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| 投影像・断面図 |
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| 密度ヒストグラム |
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試料の構成要素
-全体 : CryoEM structure of Gi-coupled MRGPRX1 with peptide agonist BAM8-22
| 全体 | 名称: CryoEM structure of Gi-coupled MRGPRX1 with peptide agonist BAM8-22 |
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| 要素 |
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-超分子 #1: CryoEM structure of Gi-coupled MRGPRX1 with peptide agonist BAM8-22
| 超分子 | 名称: CryoEM structure of Gi-coupled MRGPRX1 with peptide agonist BAM8-22 タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: all |
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| 由来(天然) | 生物種: Homo sapiens (ヒト) |
-分子 #1: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
| 分子 | 名称: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 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: Homo sapiens (ヒト) |
| 分子量 | 理論値: 6.633625 KDa |
| 組換発現 | 生物種: ![]() |
| 配列 | 文字列: NTASIAQARK LVEQLKMEAN IDRIKVSKAA ADLMAYCEAH AKEDPLLTPV PASENPFREK UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 |
-分子 #2: BAM8-22
| 分子 | 名称: BAM8-22 / 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: Homo sapiens (ヒト) |
| 分子量 | 理論値: 1.603797 KDa |
| 配列 | 文字列: PEWWMDYQKR Y UniProtKB: Proenkephalin-A |
-分子 #3: Single-Chain Fragment Variable 16
| 分子 | 名称: Single-Chain Fragment Variable 16 / タイプ: protein_or_peptide / ID: 3 / コピー数: 1 / 光学異性体: LEVO |
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| 由来(天然) | 生物種: Homo sapiens (ヒト) |
| 分子量 | 理論値: 30.363043 KDa |
| 組換発現 | 生物種: ![]() |
| 配列 | 文字列: MLLVNQSHQG FNKEHTSKMV SAIVLYVLLA AAAHSAFAVQ LVESGGGLVQ PGGSRKLSCS ASGFAFSSFG MHWVRQAPEK GLEWVAYIS SGSGTIYYAD TVKGRFTISR DDPKNTLFLQ MTSLRSEDTA MYYCVRSIYY YGSSPFDFWG QGTTLTVSAG G GGSGGGGS ...文字列: MLLVNQSHQG FNKEHTSKMV SAIVLYVLLA AAAHSAFAVQ LVESGGGLVQ PGGSRKLSCS ASGFAFSSFG MHWVRQAPEK GLEWVAYIS SGSGTIYYAD TVKGRFTISR DDPKNTLFLQ MTSLRSEDTA MYYCVRSIYY YGSSPFDFWG QGTTLTVSAG G GGSGGGGS GGGGSADIVM TQATSSVPVT PGESVSISCR SSKSLLHSNG NTYLYWFLQR PGQSPQLLIY RMSNLASGVP DR FSGSGSG TAFTLTISRL EAEDVGVYYC MQHLEYPLTF GAGTKLEL |
-分子 #4: Guanine nucleotide-binding protein G(i) subunit alpha-1
| 分子 | 名称: Guanine nucleotide-binding protein G(i) subunit alpha-1 タイプ: protein_or_peptide / ID: 4 / コピー数: 1 / 光学異性体: LEVO |
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| 由来(天然) | 生物種: Homo sapiens (ヒト) |
| 分子量 | 理論値: 40.415031 KDa |
| 組換発現 | 生物種: ![]() |
| 配列 | 文字列: MGCTLSAEDK AAVERSKMID RNLREDGEKA AREVKLLLLG AGESGKSTIV KQMKIIHEAG YSEEECKQYK AVVYSNTIQS IIAIIRAMG RLKIDFGDSA RADDARQLFV LAGAAEEGFM TAELAGVIKR LWKDSGVQAC FNRSREYQLN DSAAYYLNDL D RIAQPNYI ...文字列: MGCTLSAEDK AAVERSKMID RNLREDGEKA AREVKLLLLG AGESGKSTIV KQMKIIHEAG YSEEECKQYK AVVYSNTIQS IIAIIRAMG RLKIDFGDSA RADDARQLFV LAGAAEEGFM TAELAGVIKR LWKDSGVQAC FNRSREYQLN DSAAYYLNDL D RIAQPNYI PTQQDVLRTR VKTTGIVETH FTFKDLHFKM FDVGGQRSER KKWIHCFEGV TAIIFCVALS DYDLVLAEDE EM NRMHESM KLFDSICNNK WFTDTSIILF LNKKDLFEEK IKKSPLTICY PEYAGSNTYE EAAAYIQCQF EDLNKRKDTK EIY THFTCA TDTKNVQFVF DAVTDVIIKN NLKDCGLF UniProtKB: Guanine nucleotide-binding protein G(i) subunit alpha-1 |
-分子 #5: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
| 分子 | 名称: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 タイプ: protein_or_peptide / ID: 5 / コピー数: 1 / 光学異性体: LEVO |
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| 由来(天然) | 生物種: Homo sapiens (ヒト) |
| 分子量 | 理論値: 38.561152 KDa |
| 組換発現 | 生物種: ![]() |
| 配列 | 文字列: LEVLFQGPCG SSGSELDQLR QEAEQLKNQI RDARKACADA TLSQITNNID PVGRIQMRTR RTLRGHLAKI YAMHWGTDSR LLVSASQDG KLIIWDSYTT NKVHAIPLRS SWVMTCAYAP SGNYVACGGL DNICSIYNLK TREGNVRVSR ELAGHTGYLS C CRFLDDNQ ...文字列: LEVLFQGPCG SSGSELDQLR QEAEQLKNQI RDARKACADA TLSQITNNID PVGRIQMRTR RTLRGHLAKI YAMHWGTDSR LLVSASQDG KLIIWDSYTT NKVHAIPLRS SWVMTCAYAP SGNYVACGGL DNICSIYNLK TREGNVRVSR ELAGHTGYLS C CRFLDDNQ IVTSSGDTTC ALWDIETGQQ TTTFTGHTGD VMSLSLAPDT RLFVSGACDA SAKLWDVREG MCRQTFTGHE SD INAICFF PNGNAFATGS DDATCRLFDL RADQELMTYS HDNIICGITS VSFSKSGRLL LAGYDDFNCN VWDALKADRA GVL AGHDNR VSCLGVTDDG MAVATGSWDS FLKIWN UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 |
-分子 #6: Mas-related G-protein coupled receptor member X1
| 分子 | 名称: Mas-related G-protein coupled receptor member X1 / タイプ: protein_or_peptide / ID: 6 / コピー数: 1 / 光学異性体: LEVO |
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| 由来(天然) | 生物種: Homo sapiens (ヒト) |
| 分子量 | 理論値: 36.276906 KDa |
| 組換発現 | 生物種: ![]() |
| 配列 | 文字列: MDPTISTLDT ELTPINGTEE TLCYKQTLSL TVLTCIVSLV GLTGNAVVLW LLGCRMRRNA FSIYILNLAA ADFLFLSGRL IYSLLSFIS IPHTISKILY PVMMFSYFAG LSFLSAVSTE RCLSVLWPIW YRCHRPTHLS AVVCVLLWAL SLLRSILEWM L CGFLFSGA ...文字列: MDPTISTLDT ELTPINGTEE TLCYKQTLSL TVLTCIVSLV GLTGNAVVLW LLGCRMRRNA FSIYILNLAA ADFLFLSGRL IYSLLSFIS IPHTISKILY PVMMFSYFAG LSFLSAVSTE RCLSVLWPIW YRCHRPTHLS AVVCVLLWAL SLLRSILEWM L CGFLFSGA DSAWCQTSDF ITVAWLIFLC VVLCGSSLVL LIRILCGSRK IPLTRLYVTI LLTVLVFLLC GLPFGIQFFL FL WIHVDRE VLFCHVHLVS IFLSALNSSA NPIIYFFVGS FRQRQNRQNL KLVLQRALQD ASEVDEGGGQ LPEEILELSG SRL EQ UniProtKB: Mas-related G-protein coupled receptor member X1 |
-実験情報
-構造解析
| 手法 | クライオ電子顕微鏡法 |
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解析 | 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 K3 (6k x 4k) / 平均電子線量: 60.0 e/Å2 |
| 電子線 | 加速電圧: 300 kV / 電子線源: FIELD EMISSION GUN |
| 電子光学系 | 照射モード: FLOOD BEAM / 撮影モード: DIFFRACTION / 最大 デフォーカス(公称値): 1.2 µm / 最小 デフォーカス(公称値): 0.8 µm |
| 実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |
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画像解析
| 初期モデル | モデルのタイプ: OTHER |
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| 最終 再構成 | 解像度のタイプ: BY AUTHOR / 解像度: 3.0 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 924644 |
| 初期 角度割当 | タイプ: ANGULAR RECONSTITUTION |
| 最終 角度割当 | タイプ: ANGULAR RECONSTITUTION |
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コントローラー
万見について




キーワード
Homo sapiens (ヒト)
データ登録者
中国, 2件
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FIELD EMISSION GUN
