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基本情報
登録情報 | データベース: PDB / ID: 8t6j | |||||||||
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タイトル | CDPPB-bound inactive mGlu5 | |||||||||
![]() | Metabotropic glutamate receptor 5 | |||||||||
![]() | SIGNALING PROTEIN / GPCR | |||||||||
機能・相同性 | ![]() A2A adenosine receptor binding / phospholipase C-activating G protein-coupled glutamate receptor signaling pathway / G protein-coupled receptor activity involved in regulation of postsynaptic membrane potential / trans-synaptic signaling by endocannabinoid, modulating synaptic transmission / adenylate cyclase inhibiting G protein-coupled glutamate receptor activity / positive regulation of long-term neuronal synaptic plasticity / desensitization of G protein-coupled receptor signaling pathway / neurotransmitter receptor activity involved in regulation of postsynaptic cytosolic calcium ion concentration / G protein-coupled glutamate receptor signaling pathway / astrocyte projection ...A2A adenosine receptor binding / phospholipase C-activating G protein-coupled glutamate receptor signaling pathway / G protein-coupled receptor activity involved in regulation of postsynaptic membrane potential / trans-synaptic signaling by endocannabinoid, modulating synaptic transmission / adenylate cyclase inhibiting G protein-coupled glutamate receptor activity / positive regulation of long-term neuronal synaptic plasticity / desensitization of G protein-coupled receptor signaling pathway / neurotransmitter receptor activity involved in regulation of postsynaptic cytosolic calcium ion concentration / G protein-coupled glutamate receptor signaling pathway / astrocyte projection / Class C/3 (Metabotropic glutamate/pheromone receptors) / : / glutamate receptor activity / Neurexins and neuroligins / protein tyrosine kinase activator activity / : / regulation of synaptic transmission, glutamatergic / protein tyrosine kinase binding / dendritic shaft / learning / locomotory behavior / G protein-coupled receptor activity / postsynaptic density membrane / synapse organization / Schaffer collateral - CA1 synapse / cognition / cellular response to amyloid-beta / G alpha (q) signalling events / chemical synaptic transmission / positive regulation of MAPK cascade / dendritic spine / learning or memory / glutamatergic synapse / dendrite / regulation of DNA-templated transcription / identical protein binding / plasma membrane / 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: 3.5 Å | |||||||||
![]() | Krishna Kumar, K. / Wang, H. / Kobilka, B.K. | |||||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Stepwise activation of a metabotropic glutamate receptor. 著者: Kaavya Krishna Kumar / Haoqing Wang / Chris Habrian / Naomi R Latorraca / Jun Xu / Evan S O'Brien / Chensong Zhang / Elizabeth Montabana / Antoine Koehl / Susan Marqusee / Ehud Y Isacoff / Brian K Kobilka / ![]() 要旨: Metabotropic glutamate receptors belong to a family of G protein-coupled receptors that are obligate dimers and possess a large extracellular ligand-binding domain that is linked via a cysteine-rich ...Metabotropic glutamate receptors belong to a family of G protein-coupled receptors that are obligate dimers and possess a large extracellular ligand-binding domain that is linked via a cysteine-rich domain to their 7-transmembrane domain. Upon activation, these receptors undergo a large conformational change to transmit the ligand binding signal from the extracellular ligand-binding domain to the G protein-coupling 7-transmembrane domain. In this manuscript, we propose a model for a sequential, multistep activation mechanism of metabotropic glutamate receptor subtype 5. We present a series of structures in lipid nanodiscs, from inactive to fully active, including agonist-bound intermediate states. Further, using bulk and single-molecule fluorescence imaging, we reveal distinct receptor conformations upon allosteric modulator and G protein binding. #1: ジャーナル: bioRxiv / 年: 2023 タイトル: Step-wise activation of a Family C GPCR. 著者: Kaavya Krishna Kumar / Haoqing Wang / Chris Habrian / Naomi R Latorraca / Jun Xu / Evan S O'Brien / Chensong Zhang / Elizabeth Montabana / Antoine Koehl / Susan Marqusee / Ehud Y Isacoff / Brian K Kobilka / ![]() 要旨: Metabotropic glutamate receptors belong to a family of G protein-coupled receptors that are obligate dimers and possess a large extracellular ligand-binding domain (ECD) that is linked via a cysteine- ...Metabotropic glutamate receptors belong to a family of G protein-coupled receptors that are obligate dimers and possess a large extracellular ligand-binding domain (ECD) that is linked via a cysteine-rich domain (CRDs) to their 7-transmembrane (TM) domain. Upon activation, these receptors undergo a large conformational change to transmit the ligand binding signal from the ECD to the G protein-coupling TM. In this manuscript, we propose a model for a sequential, multistep activation mechanism of metabotropic glutamate receptor subtype 5. We present a series of structures in lipid nanodiscs, from inactive to fully active, including agonist-bound intermediate states. Further, using bulk and single-molecule fluorescence imaging we reveal distinct receptor conformations upon allosteric modulator and G protein binding. | |||||||||
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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 | ![]() | 276.1 KB | 表示 | ![]() |
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PDB形式 | ![]() | 215.9 KB | 表示 | ![]() |
PDBx/mmJSON形式 | ![]() | ツリー表示 | ![]() | |
その他 | ![]() |
-検証レポート
文書・要旨 | ![]() | 838.1 KB | 表示 | ![]() |
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文書・詳細版 | ![]() | 854.8 KB | 表示 | |
XML形式データ | ![]() | 46 KB | 表示 | |
CIF形式データ | ![]() | 68.8 KB | 表示 | |
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-関連構造データ
関連構造データ | ![]() 41069MC ![]() 8t7hC ![]() 8t8mC ![]() 8taoC ![]() 41783 ![]() 41787 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
#1: タンパク質 | 分子量: 98868.297 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: P41594 #2: 化合物 | 研究の焦点であるリガンドがあるか | Y | |
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-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: Metabotropic glutamate receptor 5 in complex with CDPPB タイプ: ORGANELLE OR CELLULAR COMPONENT / Entity ID: #1 / 由来: RECOMBINANT |
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分子量 | 実験値: NO |
由来(天然) | 生物種: ![]() |
由来(組換発現) | 生物種: ![]() ![]() |
緩衝液 | pH: 7.4 |
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: FEI TITAN 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): 2000 nm / 最小 デフォーカス(公称値): 700 nm |
撮影 | 電子線照射量: 52.2 e/Å2 フィルム・検出器のモデル: GATAN K3 BIOQUANTUM (6k x 4k) |
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解析
CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
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3次元再構成 | 解像度: 3.5 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 246232 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
精密化 | 交差検証法: NONE 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: 60.64 Å2 | ||||||||||||||||||||||||
拘束条件 |
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