+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 9asb | ||||||
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タイトル | Structure of human calcium-sensing receptor in complex with chimeric Gq (miniGisq) protein in nanodiscs | ||||||
要素 |
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キーワード | MEMBRANE PROTEIN (膜タンパク質) / Calcium-sensing receptor (カルシウム感知受容体) / G-protein-coupled receptor (Gタンパク質共役受容体) / G protein (Gタンパク質) / signal transduction (シグナル伝達) | ||||||
機能・相同性 | 機能・相同性情報 bile acid secretion / chemosensory behavior / cellular response to peptide / response to fibroblast growth factor / sensory perception of chemical stimulus / cellular response to vitamin D / mu-type opioid receptor binding / phosphatidylinositol phospholipase C activity / corticotropin-releasing hormone receptor 1 binding / Class C/3 (Metabotropic glutamate/pheromone receptors) ...bile acid secretion / chemosensory behavior / cellular response to peptide / response to fibroblast growth factor / sensory perception of chemical stimulus / cellular response to vitamin D / mu-type opioid receptor binding / phosphatidylinositol phospholipase C activity / corticotropin-releasing hormone receptor 1 binding / Class C/3 (Metabotropic glutamate/pheromone receptors) / calcium ion import / positive regulation of positive chemotaxis / beta-2 adrenergic receptor binding / fat pad development / amino acid binding / cellular response to hepatocyte growth factor stimulus / branching morphogenesis of an epithelial tube / positive regulation of calcium ion import / regulation of calcium ion transport / cellular response to low-density lipoprotein particle stimulus / detection of calcium ion / Adenylate cyclase inhibitory pathway / D1 dopamine receptor binding / positive regulation of protein localization to cell cortex / anatomical structure morphogenesis / regulation of cAMP-mediated signaling / D2 dopamine receptor binding / G protein-coupled serotonin receptor binding / axon terminus / cellular response to forskolin / regulation of mitotic spindle organization / JNK cascade / positive regulation of vasoconstriction / chloride transmembrane transport / insulin-like growth factor receptor binding / ionotropic glutamate receptor binding / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / 骨化 / Regulation of insulin secretion / G protein-coupled receptor activity / G protein-coupled receptor binding / response to ischemia / cellular response to glucose stimulus / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / Activation of the phototransduction cascade / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / G-protein activation / G protein-coupled acetylcholine receptor signaling pathway / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / positive regulation of insulin secretion / Prostacyclin signalling through prostacyclin receptor / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / ADP signalling through P2Y purinoceptor 12 / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / Sensory perception of sweet, bitter, and umami (glutamate) taste / photoreceptor disc membrane / response to peptide hormone / 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 / intracellular calcium ion homeostasis / 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 / vasodilation / GPER1 signaling / G-protein beta-subunit binding / GDP binding / Inactivation, recovery and regulation of the phototransduction cascade / heterotrimeric G-protein complex / G alpha (12/13) signalling events / extracellular vesicle / signaling receptor complex adaptor activity / integrin binding / Thrombin signalling through proteinase activated receptors (PARs) / retina development in camera-type eye / GTPase binding / phospholipase C-activating G protein-coupled receptor signaling pathway / Ca2+ pathway / 細胞皮質 / midbody / G alpha (i) signalling events / fibroblast proliferation / cellular response to hypoxia / G alpha (s) signalling events / G alpha (q) signalling events 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: 3.4 Å | ||||||
データ登録者 | Zuo, H. / Park, J. / Frangaj, A. / Ye, J. / Lu, G. / Manning, J.J. / Asher, W.B. / Lu, Z. / Hu, G. / Wang, L. ...Zuo, H. / Park, J. / Frangaj, A. / Ye, J. / Lu, G. / Manning, J.J. / Asher, W.B. / Lu, Z. / Hu, G. / Wang, L. / Mendez, J. / Eng, E. / Zhang, Z. / Lin, X. / Grasucci, R. / Hendrickson, W.A. / Clarke, O.B. / Javitch, J.A. / Conigrave, A.D. / Fan, Q.R. | ||||||
資金援助 | 米国, 1件
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引用 | ジャーナル: Nature / 年: 2024 タイトル: Promiscuous G-protein activation by the calcium-sensing receptor. 著者: Hao Zuo / Jinseo Park / Aurel Frangaj / Jianxiang Ye / Guanqi Lu / Jamie J Manning / Wesley B Asher / Zhengyuan Lu / Guo-Bin Hu / Liguo Wang / Joshua Mendez / Edward Eng / Zhening Zhang / Xin ...著者: Hao Zuo / Jinseo Park / Aurel Frangaj / Jianxiang Ye / Guanqi Lu / Jamie J Manning / Wesley B Asher / Zhengyuan Lu / Guo-Bin Hu / Liguo Wang / Joshua Mendez / Edward Eng / Zhening Zhang / Xin Lin / Robert Grassucci / Wayne A Hendrickson / Oliver B Clarke / Jonathan A Javitch / Arthur D Conigrave / Qing R Fan / 要旨: The human calcium-sensing receptor (CaSR) detects fluctuations in the extracellular Ca concentration and maintains Ca homeostasis. It also mediates diverse cellular processes not associated with Ca ...The human calcium-sensing receptor (CaSR) detects fluctuations in the extracellular Ca concentration and maintains Ca homeostasis. It also mediates diverse cellular processes not associated with Ca balance. The functional pleiotropy of CaSR arises in part from its ability to signal through several G-protein subtypes. We determined structures of CaSR in complex with G proteins from three different subfamilies: G, G and G. We found that the homodimeric CaSR of each complex couples to a single G protein through a common mode. This involves the C-terminal helix of each Gα subunit binding to a shallow pocket that is formed in one CaSR subunit by all three intracellular loops (ICL1-ICL3), an extended transmembrane helix 3 and an ordered C-terminal region. G-protein binding expands the transmembrane dimer interface, which is further stabilized by phospholipid. The restraint imposed by the receptor dimer, in combination with ICL2, enables G-protein activation by facilitating conformational transition of Gα. We identified a single Gα residue that determines G and G versus G selectivity. The length and flexibility of ICL2 allows CaSR to bind all three Gα subtypes, thereby conferring capacity for promiscuous G-protein coupling. | ||||||
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 | 9asb.cif.gz | 424.2 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb9asb.ent.gz | 表示 | PDB形式 | |
PDBx/mmJSON形式 | 9asb.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
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/as/9asb ftp://data.pdbj.org/pub/pdb/validation_reports/as/9asb | HTTPS FTP |
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-関連構造データ
関連構造データ | 43811MC 9avgC 9avlC 9axfC 9ayfC 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 (文献) |
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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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-要素
-タンパク質 , 2種, 3分子 QRB
#1: タンパク質 | 分子量: 102864.617 Da / 分子数: 2 / 由来タイプ: 組換発現 詳細: The CaSR construct consists of residues 1-903 and a Flag tag inserted after the signal peptide 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: CASR, GPRC2A, PCAR1 / 細胞株 (発現宿主): HEK293 GnTI- / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: P41180 #3: タンパク質 | | 分子量: 38413.895 Da / 分子数: 1 / 由来タイプ: 組換発現 詳細: The guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 construct contains a Flag epitope fused to the N-terminus. 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: GNB1 / 細胞株 (発現宿主): HEK293 GnTI- / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: P62873 |
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-Chimeric mini guanine nucleotide-binding protein G(i)(s)(q) subunit ... , 2種, 2分子 AG
#2: タンパク質 | 分子量: 28306.148 Da / 分子数: 1 / 由来タイプ: 組換発現 詳細: MiniG(q) alpha is a chimeric protein engineered based on the miniG(s) alpha skeleton [miniG(s)(q) alpha]. Chimeric miniG(i)(s)(q) alpha construct was designed where the N-terminal 25 amino ...詳細: MiniG(q) alpha is a chimeric protein engineered based on the miniG(s) alpha skeleton [miniG(s)(q) alpha]. Chimeric miniG(i)(s)(q) alpha construct was designed where the N-terminal 25 amino acids of G(s) alpha was replaced with the initial 18 residues of G(i1) alpha 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: GNAI1, GNAS / 細胞株 (発現宿主): HEK293 GnTl- / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: P63096, UniProt: A0A590UJY2 |
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#4: 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 / 細胞株 (発現宿主): HEK293 GnTI- / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: P59768 |
-糖 , 2種, 10分子
#5: 多糖 | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose #6: 糖 | ChemComp-NAG / |
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-非ポリマー , 6種, 14分子
#7: 化合物 | #8: 化合物 | #9: 化合物 | ChemComp-CA / #10: 化合物 | #11: 化合物 | ChemComp-Y01 / | #12: 化合物 | ChemComp-A1AF7 / ( | 分子量: 749.007 Da / 分子数: 1 / 由来タイプ: 合成 / 式: C40H77O10P |
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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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-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: Human CaSR in complex with chimeric Gq (miniGisq) protein タイプ: COMPLEX / Entity ID: #1-#4 / 由来: RECOMBINANT | |||||||||||||||||||||||||||||||||||
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分子量 | 値: 0.276 MDa / 実験値: NO | |||||||||||||||||||||||||||||||||||
由来(天然) | 生物種: Homo sapiens (ヒト) | |||||||||||||||||||||||||||||||||||
由来(組換発現) | 生物種: Homo sapiens (ヒト) / 細胞: HEK293 GnTI- | |||||||||||||||||||||||||||||||||||
緩衝液 | pH: 7.5 | |||||||||||||||||||||||||||||||||||
緩衝液成分 |
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試料 | 濃度: 3.6 mg/ml / 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES | |||||||||||||||||||||||||||||||||||
試料支持 | グリッドの材料: GOLD / グリッドのサイズ: 300 divisions/in. / グリッドのタイプ: Quantifoil R0.6/1 | |||||||||||||||||||||||||||||||||||
急速凍結 | 装置: FEI VITROBOT MARK IV / 凍結剤: ETHANE / 湿度: 100 % / 凍結前の試料温度: 277 K / 詳細: The sample was blotted for 6s before plunge-frozen. |
-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: 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 FIELDBright-field microscopy / 倍率(公称値): 105000 X / 最大 デフォーカス(公称値): 1900 nm / 最小 デフォーカス(公称値): 1200 nm / Cs: 2.7 mm / C2レンズ絞り径: 100 µm / アライメント法: COMA FREE |
試料ホルダ | 凍結剤: NITROGEN 試料ホルダーモデル: FEI TITAN KRIOS AUTOGRID HOLDER 最高温度: 100 K |
撮影 | 平均露光時間: 3 sec. / 電子線照射量: 74.9 e/Å2 フィルム・検出器のモデル: GATAN K3 BIOQUANTUM (6k x 4k) 撮影したグリッド数: 1 / 実像数: 9336 |
電子光学装置 | エネルギーフィルター名称: GIF Bioquantum / エネルギーフィルタースリット幅: 15 eV |
画像スキャン | 横: 11520 / 縦: 8184 |
-解析
EMソフトウェア |
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CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||||||
粒子像の選択 | 選択した粒子像数: 1339334 | ||||||||||||||||||||||||||||||||||||
対称性 | 点対称性: C1 (非対称) | ||||||||||||||||||||||||||||||||||||
3次元再構成 | 解像度: 3.4 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 91042 / 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 | 3D fitting-ID: 1 / Source name: PDB / タイプ: experimental model
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拘束条件 |
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