+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 7epd | |||||||||||||||
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タイトル | Cryo-EM structure of inactive mGlu2-7 heterodimer | |||||||||||||||
要素 |
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キーワード | MEMBRANE PROTEIN / Cryo-EM structure / GPCR | |||||||||||||||
機能・相同性 | 機能・相同性情報 regulation of response to drug / group II metabotropic glutamate receptor activity / intracellular glutamate homeostasis / behavioral response to nicotine / negative regulation of adenylate cyclase activity / G protein-coupled glutamate receptor signaling pathway / astrocyte projection / Class C/3 (Metabotropic glutamate/pheromone receptors) / glutamate secretion / glutamate receptor activity ...regulation of response to drug / group II metabotropic glutamate receptor activity / intracellular glutamate homeostasis / behavioral response to nicotine / negative regulation of adenylate cyclase activity / G protein-coupled glutamate receptor signaling pathway / astrocyte projection / Class C/3 (Metabotropic glutamate/pheromone receptors) / glutamate secretion / glutamate receptor activity / regulation of glutamate secretion / long-term synaptic depression / regulation of dopamine secretion / calcium channel regulator activity / regulation of synaptic transmission, glutamatergic / sarcoplasmic reticulum membrane / presynaptic modulation of chemical synaptic transmission / response to cocaine / peptidylprolyl isomerase / peptidyl-prolyl cis-trans isomerase activity / G protein-coupled receptor activity / presynaptic membrane / gene expression / G alpha (i) signalling events / scaffold protein binding / chemical synaptic transmission / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / axon / glutamatergic synapse / dendrite / plasma membrane 類似検索 - 分子機能 | |||||||||||||||
生物種 | Homo sapiens (ヒト) | |||||||||||||||
手法 | 電子顕微鏡法 / 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.9 Å | |||||||||||||||
データ登録者 | Du, J. / Wang, D. / Fan, H. / Tai, L. / Lin, S. / Han, S. / Sun, F. / Wu, B. / Zhao, Q. | |||||||||||||||
資金援助 | 中国, 4件
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引用 | ジャーナル: Nature / 年: 2021 タイトル: Structures of human mGlu2 and mGlu7 homo- and heterodimers. 著者: Juan Du / Dejian Wang / Hongcheng Fan / Chanjuan Xu / Linhua Tai / Shuling Lin / Shuo Han / Qiuxiang Tan / Xinwei Wang / Tuo Xu / Hui Zhang / Xiaojing Chu / Cuiying Yi / Peng Liu / Xiaomei ...著者: Juan Du / Dejian Wang / Hongcheng Fan / Chanjuan Xu / Linhua Tai / Shuling Lin / Shuo Han / Qiuxiang Tan / Xinwei Wang / Tuo Xu / Hui Zhang / Xiaojing Chu / Cuiying Yi / Peng Liu / Xiaomei Wang / Yu Zhou / Jean-Philippe Pin / Philippe Rondard / Hong Liu / Jianfeng Liu / Fei Sun / Beili Wu / Qiang Zhao / 要旨: The metabotropic glutamate receptors (mGlus) are involved in the modulation of synaptic transmission and neuronal excitability in the central nervous system. These receptors probably exist as both ...The metabotropic glutamate receptors (mGlus) are involved in the modulation of synaptic transmission and neuronal excitability in the central nervous system. These receptors probably exist as both homo- and heterodimers that have unique pharmacological and functional properties. Here we report four cryo-electron microscopy structures of the human mGlu subtypes mGlu2 and mGlu7, including inactive mGlu2 and mGlu7 homodimers; mGlu2 homodimer bound to an agonist and a positive allosteric modulator; and inactive mGlu2-mGlu7 heterodimer. We observed a subtype-dependent dimerization mode for these mGlus, as a unique dimer interface that is mediated by helix IV (and that is important for limiting receptor activity) exists only in the inactive mGlu2 structure. The structures provide molecular details of the inter- and intra-subunit conformational changes that are required for receptor activation, which distinguish class C G-protein-coupled receptors from those in classes A and B. Furthermore, our structure and functional studies of the mGlu2-mGlu7 heterodimer suggest that the mGlu7 subunit has a dominant role in controlling dimeric association and G-protein activation in the heterodimer. These insights into mGlu homo- and heterodimers highlight the complex landscape of mGlu dimerization and activation. | |||||||||||||||
履歴 |
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-構造の表示
ムービー |
ムービービューア |
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構造ビューア | 分子: MolmilJmol/JSmol |
-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 7epd.cif.gz | 333.6 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb7epd.ent.gz | 241.7 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 7epd.json.gz | ツリー表示 | PDBx/mmJSON形式 | |
その他 | その他のダウンロード |
-検証レポート
文書・要旨 | 7epd_validation.pdf.gz | 774.2 KB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 7epd_full_validation.pdf.gz | 785.3 KB | 表示 | |
XML形式データ | 7epd_validation.xml.gz | 40.6 KB | 表示 | |
CIF形式データ | 7epd_validation.cif.gz | 63.1 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/ep/7epd ftp://data.pdbj.org/pub/pdb/validation_reports/ep/7epd | HTTPS FTP |
-関連構造データ
-リンク
-集合体
登録構造単位 |
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1 |
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-要素
#1: タンパク質 | 分子量: 104904.000 Da / 分子数: 1 / 変異: N655Y,H815Y / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: GRM2, GPRC1B, MGLUR2, FKBP1A / 発現宿主: mammal environmental sample (環境試料) 参照: UniProt: Q14416, UniProt: Q0VDC6, peptidylprolyl isomerase |
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#2: タンパク質 | 分子量: 109243.688 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 発現宿主: mammal environmental sample (環境試料) |
Has protein modification | Y |
-実験情報
-実験
実験 | 手法: 電子顕微鏡法 |
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EM実験 | 試料の集合状態: PARTICLE / 3次元再構成法: 単粒子再構成法 |
-試料調製
構成要素 | 名称: Inactive mGlu2-7 heterodimer / タイプ: COMPLEX / Entity ID: all / 由来: RECOMBINANT |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
由来(組換発現) | 生物種: mammal environmental sample (環境試料) |
緩衝液 | pH: 7.5 |
試料 | 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES |
急速凍結 | 凍結剤: ETHANE |
-電子顕微鏡撮影
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
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顕微鏡 | モデル: FEI TITAN KRIOS |
電子銃 | 電子線源: FIELD EMISSION GUN / 加速電圧: 300 kV / 照射モード: SPOT SCAN |
電子レンズ | モード: BRIGHT FIELD |
撮影 | 電子線照射量: 2.1875 e/Å2 フィルム・検出器のモデル: GATAN K3 BIOQUANTUM (6k x 4k) |
-解析
CTF補正 | タイプ: NONE | ||||||||||||||||||||||||
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3次元再構成 | 解像度: 3.9 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 1113538 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
精密化 | 立体化学のターゲット値: GeoStd + Monomer Library + CDL v1.2 | ||||||||||||||||||||||||
原子変位パラメータ | Biso mean: 58 Å2 | ||||||||||||||||||||||||
拘束条件 |
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