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基本情報
登録情報 | データベース: PDB / ID: 8jaf | |||||||||||||||
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タイトル | Structure of Muscarinic receptor (M2R) in complex with beta-arrestin1 (Local Refine, non-cross linked) | |||||||||||||||
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![]() | SIGNALING PROTEIN/IMMUNE SYSTEM / GPCR / Arrestin / SIGNALING PROTEIN / SIGNALING PROTEIN-IMMUNE SYSTEM complex | |||||||||||||||
機能・相同性 | ![]() MAP2K and MAPK activation / Activation of SMO / Golgi Associated Vesicle Biogenesis / Lysosome Vesicle Biogenesis / AP-2 adaptor complex binding / Muscarinic acetylcholine receptors / symmetric synapse / phospholipase C-activating G protein-coupled acetylcholine receptor signaling pathway / clathrin heavy chain binding / Ub-specific processing proteases ...MAP2K and MAPK activation / Activation of SMO / Golgi Associated Vesicle Biogenesis / Lysosome Vesicle Biogenesis / AP-2 adaptor complex binding / Muscarinic acetylcholine receptors / symmetric synapse / phospholipase C-activating G protein-coupled acetylcholine receptor signaling pathway / clathrin heavy chain binding / Ub-specific processing proteases / clathrin coat of coated pit / G protein-coupled acetylcholine receptor activity / desensitization of G protein-coupled receptor signaling pathway / cholinergic synapse / Cargo recognition for clathrin-mediated endocytosis / regulation of smooth muscle contraction / inositol hexakisphosphate binding / adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathway / Clathrin-mediated endocytosis / clathrin-dependent endocytosis / G protein-coupled serotonin receptor activity / arrestin family protein binding / G protein-coupled receptor internalization / acetylcholine receptor binding / Thrombin signalling through proteinase activated receptors (PARs) / G alpha (s) signalling events / regulation of heart contraction / clathrin binding / negative regulation of Notch signaling pathway / small molecule binding / pseudopodium / phosphatidylinositol-3,4,5-trisphosphate binding / positive regulation of receptor internalization / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / asymmetric synapse / axon terminus / visual perception / presynaptic modulation of chemical synaptic transmission / G protein-coupled receptor binding / clathrin-coated endocytic vesicle membrane / response to virus / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / G protein-coupled acetylcholine receptor signaling pathway / receptor internalization / protein transport / Cargo recognition for clathrin-mediated endocytosis / Clathrin-mediated endocytosis / nervous system development / presynaptic membrane / G alpha (i) signalling events / cytoplasmic vesicle / ubiquitin-dependent protein catabolic process / chemical synaptic transmission / postsynaptic membrane / molecular adaptor activity / positive regulation of ERK1 and ERK2 cascade / positive regulation of protein phosphorylation / G protein-coupled receptor signaling pathway / neuronal cell body / glutamatergic synapse / synapse / dendrite / signal transduction / membrane / 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: 3.1 Å | |||||||||||||||
![]() | Maharana, J. / Sano, F.K. / Shihoya, W. / Banerjee, R. / Nureki, O. / Shukla, A.K. | |||||||||||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Molecular insights into atypical modes of β-arrestin interaction with seven transmembrane receptors. 著者: Jagannath Maharana / Fumiya K Sano / Parishmita Sarma / Manish K Yadav / Longhan Duan / Tomasz M Stepniewski / Madhu Chaturvedi / Ashutosh Ranjan / Vinay Singh / Sayantan Saha / Gargi Mahajan ...著者: Jagannath Maharana / Fumiya K Sano / Parishmita Sarma / Manish K Yadav / Longhan Duan / Tomasz M Stepniewski / Madhu Chaturvedi / Ashutosh Ranjan / Vinay Singh / Sayantan Saha / Gargi Mahajan / Mohamed Chami / Wataru Shihoya / Jana Selent / Ka Young Chung / Ramanuj Banerjee / Osamu Nureki / Arun K Shukla / ![]() ![]() ![]() ![]() ![]() 要旨: β-arrestins (βarrs) are multifunctional proteins involved in signaling and regulation of seven transmembrane receptors (7TMRs), and their interaction is driven primarily by agonist-induced receptor ...β-arrestins (βarrs) are multifunctional proteins involved in signaling and regulation of seven transmembrane receptors (7TMRs), and their interaction is driven primarily by agonist-induced receptor activation and phosphorylation. Here, we present seven cryo-electron microscopy structures of βarrs either in the basal state, activated by the muscarinic receptor subtype 2 (M2R) through its third intracellular loop, or activated by the βarr-biased decoy D6 receptor (D6R). Combined with biochemical, cellular, and biophysical experiments, these structural snapshots allow the visualization of atypical engagement of βarrs with 7TMRs and also reveal a structural transition in the carboxyl terminus of βarr2 from a β strand to an α helix upon activation by D6R. Our study provides previously unanticipated molecular insights into the structural and functional diversity encoded in 7TMR-βarr complexes with direct implications for exploring novel therapeutic avenues. | |||||||||||||||
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構造の表示
構造ビューア | 分子: ![]() ![]() |
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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 | ![]() 36126MC ![]() 8go9C ![]() 8j8rC ![]() 8j8vC ![]() 8j8zC ![]() 8j97C ![]() 8j9kC ![]() 8ja3C 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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集合体
登録構造単位 | ![]()
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要素
#1: タンパク質 | 分子量: 40247.270 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: P17870 |
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#2: 抗体 | 分子量: 12861.245 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() ![]() ![]() |
#3: 抗体 | 分子量: 11500.820 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() ![]() ![]() |
#4: タンパク質・ペプチド | 分子量: 983.637 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: P08172 |
研究の焦点であるリガンドがあるか | 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 |
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分子量 | 実験値: NO | ||||||||||||||||||||||||||||||
由来(天然) |
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由来(組換発現) |
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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): 1600 nm / 最小 デフォーカス(公称値): 800 nm / Cs: 2.7 mm |
試料ホルダ | 凍結剤: NITROGEN 試料ホルダーモデル: FEI TITAN KRIOS AUTOGRID HOLDER |
撮影 | 電子線照射量: 50 e/Å2 / 検出モード: COUNTING / フィルム・検出器のモデル: GATAN K3 (6k x 4k) / 実像数: 32158 |
画像スキャン | 動画フレーム数/画像: 40 |
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解析
EMソフトウェア |
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CTF補正 | タイプ: NONE | ||||||||||||||||||||||||
粒子像の選択 | 選択した粒子像数: 17218446 | ||||||||||||||||||||||||
3次元再構成 | 解像度: 3.1 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 159811 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
原子モデル構築 | プロトコル: FLEXIBLE FIT / 空間: REAL | ||||||||||||||||||||||||
原子モデル構築 | PDB-ID: 8GO8 Accession code: 8GO8 / Source name: PDB / タイプ: experimental model |