+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 7mbx | ||||||||||||
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タイトル | Human Cholecystokinin 1 receptor (CCK1R) Gs complex | ||||||||||||
要素 |
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キーワード | MEMBRANE PROTEIN/SIGNALING PROTEIN / GPCR / MEMBRANE PROTEIN / MEMBRANE PROTEIN-SIGNALING PROTEIN complex | ||||||||||||
機能・相同性 | 機能・相同性情報 cholecystokinin receptor activity / cholecystokinin signaling pathway / regulation of hormone secretion / neuropeptide hormone activity / G-protein activation / Activation of the phototransduction cascade / Glucagon-type ligand receptors / Thromboxane signalling through TP receptor / Sensory perception of sweet, bitter, and umami (glutamate) taste / G beta:gamma signalling through PI3Kgamma ...cholecystokinin receptor activity / cholecystokinin signaling pathway / regulation of hormone secretion / neuropeptide hormone activity / G-protein activation / Activation of the phototransduction cascade / Glucagon-type ligand receptors / Thromboxane signalling through TP receptor / Sensory perception of sweet, bitter, and umami (glutamate) taste / G beta:gamma signalling through PI3Kgamma / G beta:gamma signalling through CDC42 / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Ca2+ pathway / G alpha (z) signalling events / Vasopressin regulates renal water homeostasis via Aquaporins / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / Adrenaline,noradrenaline inhibits insulin secretion / ADP signalling through P2Y purinoceptor 12 / G alpha (q) signalling events / Thrombin signalling through proteinase activated receptors (PARs) / G alpha (i) signalling events / alkylglycerophosphoethanolamine phosphodiesterase activity / peptide hormone receptor binding / digestion / photoreceptor outer segment membrane / eating behavior / spectrin binding / peptide hormone binding / PKA activation in glucagon signalling / hair follicle placode formation / photoreceptor outer segment / developmental growth / D1 dopamine receptor binding / intracellular transport / Hedgehog 'off' state / adenylate cyclase-activating adrenergic receptor signaling pathway / activation of adenylate cyclase activity / cellular response to hormone stimulus / forebrain development / cardiac muscle cell apoptotic process / adenylate cyclase activator activity / photoreceptor inner segment / Peptide ligand-binding receptors / axonogenesis / trans-Golgi network membrane / peptide binding / neuron migration / G-protein beta/gamma-subunit complex binding / bone development / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / adenylate cyclase-activating G protein-coupled receptor signaling pathway / G-protein activation / hormone activity / 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 / cognition / platelet aggregation / ADP signalling through P2Y purinoceptor 12 / G beta:gamma signalling through BTK / Adrenaline,noradrenaline inhibits insulin secretion / Glucagon-type ligand receptors / Vasopressin regulates renal water homeostasis via Aquaporins / G alpha (z) signalling events / cellular response to catecholamine stimulus / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / ADORA2B mediated anti-inflammatory cytokines production / sensory perception of taste / ADP signalling through P2Y purinoceptor 1 / adenylate cyclase-activating dopamine receptor signaling pathway / G beta:gamma signalling through PI3Kgamma / cellular response to prostaglandin E stimulus / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / GPER1 signaling / G-protein beta-subunit binding / heterotrimeric G-protein complex / G alpha (12/13) signalling events / sensory perception of smell / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / GTPase binding / retina development in camera-type eye / cellular response to hypoxia / Ca2+ pathway / positive regulation of cold-induced thermogenesis / phospholipase C-activating G protein-coupled receptor signaling pathway / positive regulation of cytosolic calcium ion concentration / G alpha (i) signalling events / cell body / fibroblast proliferation / G alpha (s) signalling events / G alpha (q) signalling events / Extra-nuclear estrogen signaling / cell population proliferation 類似検索 - 分子機能 | ||||||||||||
生物種 | Homo sapiens (ヒト) Rattus norvegicus (ドブネズミ) Lama glama (ラマ) | ||||||||||||
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: 1.95 Å | ||||||||||||
データ登録者 | Mobbs, J.I. / Belousoff, M.J. / Danev, R. / Thal, D.M. / Sexton, P.M. | ||||||||||||
資金援助 | オーストラリア, 日本, 3件
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引用 | ジャーナル: PLoS Biol / 年: 2021 タイトル: Structures of the human cholecystokinin 1 (CCK1) receptor bound to Gs and Gq mimetic proteins provide insight into mechanisms of G protein selectivity. 著者: Jesse I Mobbs / Matthew J Belousoff / Kaleeckal G Harikumar / Sarah J Piper / Xiaomeng Xu / Sebastian G B Furness / Hari Venugopal / Arthur Christopoulos / Radostin Danev / Denise Wootten / ...著者: Jesse I Mobbs / Matthew J Belousoff / Kaleeckal G Harikumar / Sarah J Piper / Xiaomeng Xu / Sebastian G B Furness / Hari Venugopal / Arthur Christopoulos / Radostin Danev / Denise Wootten / David M Thal / Laurence J Miller / Patrick M Sexton / 要旨: G protein-coupled receptors (GPCRs) are critical regulators of cellular function acting via heterotrimeric G proteins as their primary transducers with individual GPCRs capable of pleiotropic ...G protein-coupled receptors (GPCRs) are critical regulators of cellular function acting via heterotrimeric G proteins as their primary transducers with individual GPCRs capable of pleiotropic coupling to multiple G proteins. Structural features governing G protein selectivity and promiscuity are currently unclear. Here, we used cryo-electron microscopy (cryo-EM) to determine structures of the cholecystokinin (CCK) type 1 receptor (CCK1R) bound to the CCK peptide agonist, CCK-8 and 2 distinct transducer proteins, its primary transducer Gq, and the more weakly coupled Gs. As seen with other Gq/11-GPCR complexes, the Gq-α5 helix (αH5) bound to a relatively narrow pocket in the CCK1R core. Surprisingly, the backbone of the CCK1R and volume of the G protein binding pocket were essentially equivalent when Gs was bound, with the Gs αH5 displaying a conformation that arises from "unwinding" of the far carboxyl-terminal residues, compared to canonically Gs coupled receptors. Thus, integrated changes in the conformations of both the receptor and G protein are likely to play critical roles in the promiscuous coupling of individual GPCRs. #1: ジャーナル: Biorxiv / 年: 2021 タイトル: Structures of the human cholecystokinin 1 (CCK1) receptor bound to Gs and Gq mimetic proteins: insight into mechanisms of G protein selectivity 著者: Mobbs, J. / Belousoff, M.J. / Harikumar, K.G. / Piper, S.J. / Xu, X. / Furness, S.G.B. / Venugopal, H. / Christopoulos, A. / Danev, R. / Wootten, D. / Thal, D.M. / Miller, L.J. / Sexton, P.M. | ||||||||||||
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 | 7mbx.cif.gz | 202.2 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb7mbx.ent.gz | 160.9 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 7mbx.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 | 7mbx_validation.pdf.gz | 1.2 MB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 7mbx_full_validation.pdf.gz | 1.2 MB | 表示 | |
XML形式データ | 7mbx_validation.xml.gz | 43.6 KB | 表示 | |
CIF形式データ | 7mbx_validation.cif.gz | 65.7 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/mb/7mbx ftp://data.pdbj.org/pub/pdb/validation_reports/mb/7mbx | 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
-Guanine nucleotide-binding protein ... , 3種, 3分子 ABG
#1: タンパク質 | 分子量: 45699.434 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: GNAS, GNAS1, GSP / 発現宿主: Trichoplusia ni (イラクサキンウワバ) / 参照: UniProt: P63092 |
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#2: タンパク質 | 分子量: 37416.930 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Rattus norvegicus (ドブネズミ) / 遺伝子: Gnb1 / 発現宿主: Trichoplusia ni (イラクサキンウワバ) / 参照: UniProt: P54311 |
#3: タンパク質 | 分子量: 7861.143 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: GNG2 / 発現宿主: Trichoplusia ni (イラクサキンウワバ) / 参照: UniProt: P59768 |
-抗体 / タンパク質・ペプチド / タンパク質 , 3種, 3分子 NPR
#4: 抗体 | 分子量: 15140.742 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Lama glama (ラマ) / 発現宿主: Escherichia coli (大腸菌) |
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#5: タンパク質・ペプチド | 分子量: 1142.262 Da / 分子数: 1 / 由来タイプ: 合成 / 由来: (合成) Homo sapiens (ヒト) / 参照: UniProt: P06307 |
#6: タンパク質 | 分子量: 48860.027 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: CCKAR, CCKRA / 発現宿主: Trichoplusia ni (イラクサキンウワバ) / 参照: UniProt: P32238 |
-非ポリマー , 2種, 62分子
#7: 化合物 | ChemComp-Y01 / |
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#8: 水 | ChemComp-HOH / |
-詳細
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 |
-試料調製
構成要素 |
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分子量 | 値: 140 kDa/nm / 実験値: YES | |||||||||||||||||||||||||||||||||||||||||||||||||
由来(天然) |
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由来(組換発現) |
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緩衝液 | pH: 7.5 | |||||||||||||||||||||||||||||||||||||||||||||||||
試料 | 濃度: 4.1 mg/ml / 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 |
撮影 | 電子線照射量: 70.56 e/Å2 フィルム・検出器のモデル: GATAN K3 BIOQUANTUM (6k x 4k) |
-解析
ソフトウェア | 名称: PHENIX / バージョン: 1.19.2_4158: / 分類: 精密化 | ||||||||||||||||||||||||
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CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3次元再構成 | 解像度: 1.95 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 643000 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
拘束条件 |
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