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基本情報
登録情報 | ![]() | |||||||||
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タイトル | Structure of human calcium-sensing receptor in complex with Gi1 (miniGi1) protein in detergent | |||||||||
![]() | Human CaSR-miniGi1 complex in detergent, composite map of locally refined CaSR ECD, CaSR TMD and G protein. | |||||||||
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![]() | Calcium-sensing receptor / G-protein-coupled receptor / G protein / signal transduction / MEMBRANE PROTEIN | |||||||||
機能・相同性 | ![]() bile acid secretion / chemosensory behavior / response to fibroblast growth factor / cellular response to peptide / cellular response to vitamin D / phosphatidylinositol phospholipase C activity / Class C/3 (Metabotropic glutamate/pheromone receptors) / calcium ion import / positive regulation of positive chemotaxis / cellular response to low-density lipoprotein particle stimulus ...bile acid secretion / chemosensory behavior / response to fibroblast growth factor / cellular response to peptide / cellular response to vitamin D / phosphatidylinositol phospholipase C activity / Class C/3 (Metabotropic glutamate/pheromone receptors) / calcium ion import / positive regulation of positive chemotaxis / cellular response to low-density lipoprotein particle stimulus / fat pad development / cellular response to hepatocyte growth factor stimulus / amino acid binding / branching morphogenesis of an epithelial tube / positive regulation of calcium ion import / regulation of calcium ion transport / positive regulation of vasoconstriction / detection of calcium ion / anatomical structure morphogenesis / Adenylate cyclase inhibitory pathway / positive regulation of protein localization to cell cortex / regulation of cAMP-mediated signaling / D2 dopamine receptor binding / G protein-coupled serotonin receptor binding / ossification / axon terminus / JNK cascade / regulation of mitotic spindle organization / cellular response to forskolin / chloride transmembrane transport / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / response to ischemia / Regulation of insulin secretion / G protein-coupled receptor binding / G protein-coupled receptor activity / 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 / vasodilation / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / positive regulation of insulin secretion / 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 / response to peptide hormone / 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 / Adrenaline,noradrenaline inhibits insulin secretion / Glucagon-type ligand receptors / Vasopressin regulates renal water homeostasis via Aquaporins / intracellular calcium ion homeostasis / 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 / integrin binding / 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 / GDP binding / G-protein beta-subunit 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 / Thrombin signalling through proteinase activated receptors (PARs) / GTPase binding / retina development in camera-type eye / cellular response to hypoxia / Ca2+ pathway / phospholipase C-activating G protein-coupled receptor signaling pathway / cell cortex / basolateral plasma membrane / midbody / G alpha (i) signalling events / fibroblast proliferation / G alpha (s) signalling events / G alpha (q) signalling events / Ras protein signal transduction / Extra-nuclear estrogen signaling / transmembrane transporter binding / cell population proliferation / positive regulation of ERK1 and ERK2 cascade / apical plasma membrane 類似検索 - 分子機能 | |||||||||
生物種 | ![]() ![]() ![]() | |||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.6 Å | |||||||||
![]() | Zuo H / Park J / Frangaj A / Ye J / Lu G / Manning JJ / Asher WB / Lu Z / Hu G / Wang L ...Zuo H / Park J / Frangaj A / Ye J / Lu G / Manning JJ / Asher WB / Lu Z / Hu G / Wang L / Mendez J / Eng E / Zhang Z / Lin X / Grasucci R / Hendrickson WA / Clarke OB / Javitch JA / Conigrave AD / Fan QR | |||||||||
資金援助 | ![]()
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![]() | ![]() 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. | |||||||||
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画像 | ![]() | 92.9 KB | ||
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「今月の分子」の関連する項目 |
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マップ
ファイル | ![]() | ||||||||||||||||||||
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注釈 | Human CaSR-miniGi1 complex in detergent, composite map of locally refined CaSR ECD, CaSR TMD and G protein. | ||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 0.844 Å | ||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||
詳細 | EMDB XML:
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-添付データ
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試料の構成要素
+全体 : Human CaSR in complex with miniGi1 protein in detergent
+超分子 #1: Human CaSR in complex with miniGi1 protein in detergent
+分子 #1: Isoform 1 of Extracellular calcium-sensing receptor
+分子 #2: Single-chain antibody fragment scFv16
+分子 #3: Guanine nucleotide-binding protein G(i) subunit alpha-1
+分子 #4: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
+分子 #5: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
+分子 #7: 2-acetamido-2-deoxy-beta-D-glucopyranose
+分子 #8: CYCLOMETHYLTRYPTOPHAN
+分子 #9: PHOSPHATE ION
+分子 #10: CALCIUM ION
+分子 #11: 3-(2-chlorophenyl)-N-[(1R)-1-(3-methoxyphenyl)ethyl]propan-1-amine
+分子 #12: Lauryl Maltose Neopentyl Glycol
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
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![]() | 単粒子再構成法 |
試料の集合状態 | particle |
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試料調製
濃度 | 3.5 mg/mL | |||||||||||||||||||||||||||
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緩衝液 | pH: 7.5 構成要素:
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グリッド | モデル: Quantifoil R0.6/1 / 材質: GOLD / メッシュ: 300 / 支持フィルム - 材質: GOLD / 支持フィルム - トポロジー: HOLEY / 支持フィルム - Film thickness: 50 / 前処理 - タイプ: GLOW DISCHARGE / 前処理 - 時間: 25 sec. / 前処理 - 雰囲気: OTHER | |||||||||||||||||||||||||||
凍結 | 凍結剤: ETHANE / チャンバー内湿度: 100 % / チャンバー内温度: 277 K / 装置: FEI VITROBOT MARK IV 詳細: The sample was blotted for 6s before plunge-frozen.. |
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電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
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温度 | 最高: 100.0 K |
特殊光学系 | 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: 20 eV |
ソフトウェア | 名称: Leginon (ver. 3.6) |
撮影 | フィルム・検出器のモデル: GATAN K3 BIOQUANTUM (6k x 4k) デジタル化 - サイズ - 横: 5760 pixel / デジタル化 - サイズ - 縦: 4092 pixel / 撮影したグリッド数: 1 / 実像数: 15713 / 平均露光時間: 2.5 sec. / 平均電子線量: 70.14 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: ![]() |
電子光学系 | C2レンズ絞り径: 100.0 µm / 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELD / Cs: 2.7 mm / 最大 デフォーカス(公称値): 1.8 µm / 最小 デフォーカス(公称値): 1.0 µm / 倍率(公称値): 105000 |
試料ステージ | 試料ホルダーモデル: FEI TITAN KRIOS AUTOGRID HOLDER ホルダー冷却材: NITROGEN |
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |
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画像解析
-原子モデル構築 1
初期モデル |
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ソフトウェア | 名称: ![]() | ||||||||||||||
精密化 | 空間: REAL / プロトコル: FLEXIBLE FIT | ||||||||||||||
得られたモデル | ![]() PDB-9ayf: |