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基本情報
登録情報 | データベース: PDB / ID: 9ii3 | |||||||||||||||
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タイトル | Cryo-EM Structure of the 2:1 Complex of mGlu3 and beta-arrestin1 | |||||||||||||||
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![]() | MEMBRANE PROTEIN / complex | |||||||||||||||
機能・相同性 | ![]() group II metabotropic glutamate receptor activity / angiotensin receptor binding / TGFBR3 regulates TGF-beta signaling / Activation of SMO / negative regulation of interleukin-8 production / G protein-coupled glutamate receptor signaling pathway / negative regulation of adenylate cyclase activity / astrocyte projection / G protein-coupled receptor internalization / Class C/3 (Metabotropic glutamate/pheromone receptors) ...group II metabotropic glutamate receptor activity / angiotensin receptor binding / TGFBR3 regulates TGF-beta signaling / Activation of SMO / negative regulation of interleukin-8 production / G protein-coupled glutamate receptor signaling pathway / negative regulation of adenylate cyclase activity / astrocyte projection / G protein-coupled receptor internalization / Class C/3 (Metabotropic glutamate/pheromone receptors) / arrestin family protein binding / glutamate receptor activity / Lysosome Vesicle Biogenesis / Golgi Associated Vesicle Biogenesis / cellular response to stress / positive regulation of Rho protein signal transduction / stress fiber assembly / positive regulation of cardiac muscle hypertrophy / negative regulation of NF-kappaB transcription factor activity / pseudopodium / negative regulation of interleukin-6 production / enzyme inhibitor activity / positive regulation of receptor internalization / negative regulation of Notch signaling pathway / postsynaptic modulation of chemical synaptic transmission / regulation of synaptic transmission, glutamatergic / clathrin-coated pit / insulin-like growth factor receptor binding / calcium channel regulator activity / negative regulation of protein ubiquitination / cytoplasmic vesicle membrane / GTPase activator activity / Activated NOTCH1 Transmits Signal to the Nucleus / G protein-coupled receptor binding / Signaling by high-kinase activity BRAF mutants / MAP2K and MAPK activation / G protein-coupled receptor activity / Signaling by RAF1 mutants / Signaling by moderate kinase activity BRAF mutants / Paradoxical activation of RAF signaling by kinase inactive BRAF / Signaling downstream of RAS mutants / Signaling by BRAF and RAF1 fusions / endocytic vesicle membrane / protein transport / Cargo recognition for clathrin-mediated endocytosis / Thrombin signalling through proteinase activated receptors (PARs) / Clathrin-mediated endocytosis / positive regulation of protein phosphorylation / presynaptic membrane / ubiquitin-dependent protein catabolic process / cytoplasmic vesicle / scaffold protein binding / G alpha (i) signalling events / G alpha (s) signalling events / gene expression / chemical synaptic transmission / molecular adaptor activity / dendritic spine / proteasome-mediated ubiquitin-dependent protein catabolic process / postsynaptic membrane / transcription coactivator activity / positive regulation of ERK1 and ERK2 cascade / postsynaptic density / Ub-specific processing proteases / protein ubiquitination / nuclear body / axon / Golgi membrane / lysosomal membrane / ubiquitin protein ligase binding / regulation of transcription by RNA polymerase II / chromatin / glutamatergic synapse / signal transduction / positive regulation of transcription by RNA polymerase II / nucleoplasm / nucleus / plasma membrane / cytosol / cytoplasm 類似検索 - 分子機能 | |||||||||||||||
生物種 | ![]() ![]() ![]() | |||||||||||||||
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 | |||||||||||||||
![]() | Wen, T.L. / Du, M. / Yang, X. / Shen, Y.Q. | |||||||||||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Molecular basis of β-arrestin coupling to the metabotropic glutamate receptor mGlu3. 著者: Tianlei Wen / Mei Du / Yue Lu / Nan Jia / Xuhang Lu / Ning Liu / Shenghai Chang / Xing Zhang / Yuequan Shen / Xue Yang / ![]() 要旨: β-Arrestins (βarrs) mediate the desensitization and internalization of activated G-protein-coupled receptors (GPCRs). The molecular mechanism by which dimeric family C GPCR members recruit ...β-Arrestins (βarrs) mediate the desensitization and internalization of activated G-protein-coupled receptors (GPCRs). The molecular mechanism by which dimeric family C GPCR members recruit arrestins remains elusive. Here we report two structures of metabotropic glutamate receptor subtype 3 (mGlu3) coupled to βarr1, with stoichiometries of 2:1 and 2:2. The L-glutamate-bound mGlu3 dimer adopts an inactive state, with both Venus flytrap domains closed, engaging βarr1 either asymmetrically or symmetrically. The transmembrane domain of the mGlu3 protomer interacts with βarr1 through a binding pocket formed by three intracellular loops and an ordered C-terminal region. Three phosphorylation sites (pS857, pS859 and pT860) on the C-terminal tail of mGlu3 engage the N domain of βarr1. βarr1 stabilizes mGlu3 in an inactive conformation, characterized by a TM3/TM4-TM3/TM4 dimeric interface, previously observed in the negative allosteric modulator-bound structure of mGlu3. Our findings provide important insights into βarr-mediated inactivation of family C GPCRs. | |||||||||||||||
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構造の表示
構造ビューア | 分子: ![]() ![]() |
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ダウンロードとリンク
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PDBx/mmCIF形式 | ![]() | 387.6 KB | 表示 | ![]() |
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PDB形式 | ![]() | 303.9 KB | 表示 | ![]() |
PDBx/mmJSON形式 | ![]() | ツリー表示 | ![]() | |
その他 | ![]() |
-検証レポート
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
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-関連構造データ
関連構造データ | ![]() 60589MC ![]() 9ii2C M: このデータのモデリングに利用したマップデータ C: 同じ文献を引用 ( |
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類似構造データ | 類似検索 - 機能・相同性 ![]() |
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リンク
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集合体
登録構造単位 | ![]()
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要素
-タンパク質 , 2種, 3分子 RBA
#1: タンパク質 | 分子量: 99301.766 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() 発現宿主: ![]() ![]() 参照: UniProt: Q14832 #2: タンパク質 | | 分子量: 47067.332 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() 発現宿主: ![]() ![]() 参照: UniProt: P49407 |
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-抗体 / 糖 , 2種, 3分子 S
#3: 抗体 | 分子量: 26986.742 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() 発現宿主: ![]() ![]() |
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#4: 多糖 |
-非ポリマー , 2種, 4分子 


#5: 化合物 | #6: 化合物 | |
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-詳細
研究の焦点であるリガンドがあるか | N |
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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 |
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試料調製
構成要素 | 名称: GPCR/beta-arrestin/scFv30 complex / タイプ: COMPLEX / Entity ID: #1-#3 / 由来: RECOMBINANT |
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分子量 | 値: 0.15 MDa / 実験値: YES |
由来(天然) | 生物種: ![]() |
由来(組換発現) | 生物種: ![]() ![]() |
緩衝液 | pH: 7.2 |
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 |
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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: TFS KRIOS |
電子銃 | 電子線源: ![]() |
電子レンズ | モード: BRIGHT FIELD / 最大 デフォーカス(公称値): 1900 nm / 最小 デフォーカス(公称値): 600 nm |
撮影 | 電子線照射量: 50 e/Å2 フィルム・検出器のモデル: FEI FALCON IV (4k x 4k) |
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解析
CTF補正 | 詳細: CtfFind 4.1.8 / 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: 39446 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
拘束条件 |
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