+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 8uqo | |||||||||
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タイトル | PLCb3-Gbg-Gaq complex on membranes | |||||||||
要素 |
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キーワード | SIGNALING PROTEIN / PLCb3 / Gbg / Gaq | |||||||||
機能・相同性 | 機能・相同性情報 phosphoinositide phospholipase C / Fatty Acids bound to GPR40 (FFAR1) regulate insulin secretion / Acetylcholine regulates insulin secretion / phosphatidylinositol metabolic process / PLC beta mediated events / phospholipase C-activating dopamine receptor signaling pathway / entrainment of circadian clock / regulation of systemic arterial blood pressure / regulation of platelet activation / phospholipase C activity ...phosphoinositide phospholipase C / Fatty Acids bound to GPR40 (FFAR1) regulate insulin secretion / Acetylcholine regulates insulin secretion / phosphatidylinositol metabolic process / PLC beta mediated events / phospholipase C-activating dopamine receptor signaling pathway / entrainment of circadian clock / regulation of systemic arterial blood pressure / regulation of platelet activation / phospholipase C activity / phototransduction, visible light / phosphatidylinositol phospholipase C activity / regulation of canonical Wnt signaling pathway / glutamate receptor signaling pathway / postsynaptic cytosol / Synthesis of IP3 and IP4 in the cytosol / action potential / phosphatidylinositol-mediated signaling / photoreceptor outer segment / lipid catabolic process / release of sequestered calcium ion into cytosol / GTPase activator activity / molecular function activator activity / G protein-coupled receptor binding / negative regulation of protein kinase activity / G-protein beta/gamma-subunit complex binding / adenylate cyclase-activating G protein-coupled receptor signaling pathway / Olfactory Signaling Pathway / Activation of the phototransduction cascade / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / G protein-coupled acetylcholine receptor signaling pathway / G-protein activation / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Prostacyclin signalling through prostacyclin receptor / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / Sensory perception of sweet, bitter, and umami (glutamate) taste / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / photoreceptor disc membrane / Glucagon-type ligand receptors / Adrenaline,noradrenaline inhibits insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / G alpha (z) signalling events / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / cellular response to catecholamine stimulus / ADORA2B mediated anti-inflammatory cytokines production / sensory perception of taste / ADP signalling through P2Y purinoceptor 1 / 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 / blood coagulation / cellular response to prostaglandin E stimulus / Inactivation, recovery and regulation of the phototransduction cascade / G-protein beta-subunit binding / heterotrimeric G-protein complex / G alpha (12/13) signalling events / extracellular vesicle / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / GTPase binding / retina development in camera-type eye / Ca2+ pathway / phospholipase C-activating G protein-coupled receptor signaling pathway / G alpha (i) signalling events / 加水分解酵素; 酸無水物に作用; GTPに作用・細胞または細胞小器官の運動に関与 / G alpha (s) signalling events / nuclear membrane / G alpha (q) signalling events / Ras protein signal transduction / cell population proliferation / Extra-nuclear estrogen signaling / molecular adaptor activity / calmodulin binding / protein stabilization / cadherin binding / G protein-coupled receptor signaling pathway / lysosomal membrane / GTPase activity / calcium ion binding / synapse / protein-containing complex binding / GTP binding / Golgi apparatus / signal transduction / protein-containing complex / extracellular exosome / membrane / nucleus / metal ion binding / plasma membrane / cytosol / cytoplasm 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: 3.37 Å | |||||||||
データ登録者 | Falzone, M.E. / MacKinnon, R. | |||||||||
資金援助 | 米国, 2件
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引用 | ジャーナル: Proc Natl Acad Sci U S A / 年: 2023 タイトル: The mechanism of regulation of -catalyzed hydrolysis. 著者: Maria E Falzone / Roderick MacKinnon / 要旨: () enzymes cleave phosphatidylinositol 4,5-bisphosphate ( producing and (diacylglycerol). modulates the function of many ion channels, while and regulate intracellular Ca levels and protein ... () enzymes cleave phosphatidylinositol 4,5-bisphosphate ( producing and (diacylglycerol). modulates the function of many ion channels, while and regulate intracellular Ca levels and protein phosphorylation by protein kinase C, respectively. enzymes are under the control of G protein coupled receptor signaling through direct interactions with G proteins and and have been shown to be coincidence detectors for dual stimulation of and -coupled receptors. are aqueous-soluble cytoplasmic enzymes but partition onto the membrane surface to access their lipid substrate, complicating their functional and structural characterization. Using newly developed methods, we recently showed that activates by recruiting it to the membrane. Using these same methods, here we show that increases the catalytic rate constant, , of . Since stimulation of by depends on an autoinhibitory element (the X-Y linker), we propose that produces partial relief of the X-Y linker autoinhibition through an allosteric mechanism. We also determined membrane-bound structures of the and complexes, which show that these G proteins can bind simultaneously and independently of each other to regulate activity. The structures rationalize a finding in the enzyme assay, that costimulation by both G proteins follows a product rule of each independent stimulus. We conclude that baseline activity of is strongly suppressed, but the effect of G proteins, especially acting together, provides a robust stimulus upon G protein stimulation. | |||||||||
履歴 |
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-構造の表示
構造ビューア | 分子: MolmilJmol/JSmol |
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-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 8uqo.cif.gz | 379.9 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb8uqo.ent.gz | 289.7 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 8uqo.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 | 8uqo_validation.pdf.gz | 1.6 MB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 8uqo_full_validation.pdf.gz | 1.6 MB | 表示 | |
XML形式データ | 8uqo_validation.xml.gz | 60.3 KB | 表示 | |
CIF形式データ | 8uqo_validation.cif.gz | 90 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/uq/8uqo ftp://data.pdbj.org/pub/pdb/validation_reports/uq/8uqo | HTTPS FTP |
-関連構造データ
関連構造データ | 42476MC 8uqnC C: 同じ文献を引用 (文献) M: このデータのモデリングに利用したマップデータ |
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類似構造データ | 類似検索 - 機能・相同性F&H 検索 |
-リンク
-集合体
登録構造単位 |
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1 |
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-要素
-Guanine nucleotide-binding protein ... , 3種, 5分子 BCDGA
#1: タンパク質 | 分子量: 37416.930 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: GNB1 / 発現宿主: Trichoplusia ni (イラクサキンウワバ) / 参照: UniProt: P62873 #2: タンパク質 | 分子量: 8015.310 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: GNG2 / 発現宿主: Trichoplusia ni (イラクサキンウワバ) / 参照: UniProt: G3V2N0 #3: タンパク質 | | 分子量: 41676.387 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: GNAQ / 発現宿主: Trichoplusia ni (イラクサキンウワバ) / 参照: UniProt: P50148 |
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-タンパク質 , 1種, 1分子 Q
#4: タンパク質 | 分子量: 139104.719 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: PLCB3 / 発現宿主: Trichoplusia ni (イラクサキンウワバ) / 参照: UniProt: Q01970, phosphoinositide phospholipase C |
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-非ポリマー , 5種, 5分子
#5: 化合物 | ChemComp-GDP / |
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#6: 化合物 | ChemComp-ALF / |
#7: 化合物 | ChemComp-MG / |
#8: 化合物 | ChemComp-CA / |
#9: 水 | ChemComp-HOH / |
-詳細
研究の焦点であるリガンドがあるか | N |
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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 |
-試料調製
構成要素 | 名称: PLCb3-Gbg-Gaq complex / タイプ: COMPLEX / Entity ID: #1-#4 / 由来: RECOMBINANT |
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分子量 | 実験値: NO |
由来(天然) | 生物種: Homo sapiens (ヒト) |
由来(組換発現) | 生物種: Trichoplusia ni (イラクサキンウワバ) |
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 |
-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: FIELD EMISSION GUN / 加速電圧: 300 kV / 照射モード: FLOOD BEAM |
電子レンズ | モード: BRIGHT FIELD / 最大 デフォーカス(公称値): 2500 nm / 最小 デフォーカス(公称値): 1500 nm |
撮影 | 電子線照射量: 60 e/Å2 / フィルム・検出器のモデル: GATAN K3 (6k x 4k) |
-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: 3.37 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 359215 / 対称性のタイプ: POINT |