+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 7xms | |||||||||||||||||||||||||||
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タイトル | CryoEM structure of somatostatin receptor 4 (SSTR4) in complex with Gi1 and its endogeneous ligand SST-14 | |||||||||||||||||||||||||||
要素 |
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キーワード | SIGNALING PROTEIN / G protein-coupled receptor (Gタンパク質共役受容体) / somatostatin receptor 4 / cryo-EM (低温電子顕微鏡法) / STRUCTURAL PROTEIN (タンパク質) | |||||||||||||||||||||||||||
機能・相同性 | 機能・相同性情報 somatostatin signaling pathway / MECP2 regulates transcription of neuronal ligands / somatostatin receptor activity / hormone-mediated apoptotic signaling pathway / positive regulation of arachidonic acid secretion / negative regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / neuropeptide binding / hyperosmotic response / response to acidic pH / cellular response to glucocorticoid stimulus ...somatostatin signaling pathway / MECP2 regulates transcription of neuronal ligands / somatostatin receptor activity / hormone-mediated apoptotic signaling pathway / positive regulation of arachidonic acid secretion / negative regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / neuropeptide binding / hyperosmotic response / response to acidic pH / cellular response to glucocorticoid stimulus / response to steroid hormone / neuronal dense core vesicle / regulation of postsynaptic membrane neurotransmitter receptor levels / plasma membrane => GO:0005886 / G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger / neuropeptide signaling pathway / Adenylate cyclase inhibitory pathway / GABA-ergic synapse / positive regulation of protein localization to cell cortex / regulation of cAMP-mediated signaling / response to amino acid / D2 dopamine receptor binding / G protein-coupled serotonin receptor binding / forebrain development / regulation of mitotic spindle organization / cellular response to forskolin / regulation of cell migration / 消化 / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / Peptide ligand-binding receptors / response to nutrient / Regulation of insulin secretion / G protein-coupled receptor activity / G protein-coupled receptor binding / peptide binding / 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 / Prostacyclin signalling through prostacyclin receptor / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / hormone activity / 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 / 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 / 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 / 遊走 / Thrombin signalling through proteinase activated receptors (PARs) / retina development in camera-type eye / GTPase binding / cell-cell signaling / phospholipase C-activating G protein-coupled receptor signaling pathway / Ca2+ pathway / 細胞皮質 / midbody / G alpha (i) signalling events / fibroblast proliferation / G alpha (s) signalling events / G alpha (q) signalling events / chemical synaptic transmission / cell population proliferation / Ras protein signal transduction / Extra-nuclear estrogen signaling / cell surface receptor signaling pathway / positive regulation of ERK1 and ERK2 cascade / response to xenobiotic stimulus / neuron projection / G protein-coupled receptor signaling pathway / 細胞周期 類似検索 - 分子機能 | |||||||||||||||||||||||||||
生物種 | Homo sapiens (ヒト) Mus musculus (ハツカネズミ) | |||||||||||||||||||||||||||
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: 2.9 Å | |||||||||||||||||||||||||||
データ登録者 | Wenli, Z. / Shuo, H. / Na, Q. / Wenbo, Z. / Mengjie, L. / Dehua, Y. / Ming-Wei, W. / Wu, B. / Zhao, Q. | |||||||||||||||||||||||||||
資金援助 | 中国, 8件
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引用 | ジャーナル: Cell Res / 年: 2022 タイトル: Structural insights into ligand recognition and selectivity of somatostatin receptors. 著者: Wenli Zhao / Shuo Han / Na Qiu / Wenbo Feng / Mengjie Lu / Wenru Zhang / Mu Wang / Qingtong Zhou / Shutian Chen / Wei Xu / Juan Du / Xiaojing Chu / Cuiying Yi / Antao Dai / Liaoyuan Hu / ...著者: Wenli Zhao / Shuo Han / Na Qiu / Wenbo Feng / Mengjie Lu / Wenru Zhang / Mu Wang / Qingtong Zhou / Shutian Chen / Wei Xu / Juan Du / Xiaojing Chu / Cuiying Yi / Antao Dai / Liaoyuan Hu / Michelle Y Shen / Yaping Sun / Qing Zhang / Yingli Ma / Wenge Zhong / Dehua Yang / Ming-Wei Wang / Beili Wu / Qiang Zhao / 要旨: Somatostatin receptors (SSTRs) play versatile roles in inhibiting the secretion of multiple hormones such as growth hormone and thyroid-stimulating hormone, and thus are considered as targets for ...Somatostatin receptors (SSTRs) play versatile roles in inhibiting the secretion of multiple hormones such as growth hormone and thyroid-stimulating hormone, and thus are considered as targets for treating multiple tumors. Despite great progress made in therapeutic development against this diverse receptor family, drugs that target SSTRs still show limited efficacy with preferential binding affinity and conspicuous side-effects. Here, we report five structures of SSTR2 and SSTR4 in different states, including two crystal structures of SSTR2 in complex with a selective peptide antagonist and a non-peptide agonist, respectively, a cryo-electron microscopy (cryo-EM) structure of G-bound SSTR2 in the presence of the endogenous ligand SST-14, as well as two cryo-EM structures of G-bound SSTR4 in complex with SST-14 and a small-molecule agonist J-2156, respectively. By comparison of the SSTR structures in different states, molecular mechanisms of agonism and antagonism were illustrated. Together with computational and functional analyses, the key determinants responsible for ligand recognition and selectivity of different SSTR subtypes and multiform binding modes of peptide and non-peptide ligands were identified. Insights gained in this study will help uncover ligand selectivity of various SSTRs and accelerate the development of new molecules with better efficacy by targeting SSTRs. | |||||||||||||||||||||||||||
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 | 7xms.cif.gz | 208.5 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb7xms.ent.gz | 156.8 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 7xms.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/xm/7xms ftp://data.pdbj.org/pub/pdb/validation_reports/xm/7xms | HTTPS FTP |
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-関連構造データ
関連構造データ | 33303MC 7xmrC 7xmtC 7xn9C 7xnaC 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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1 |
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-要素
-Guanine nucleotide-binding protein ... , 3種, 3分子 ABC
#2: タンパク質 | 分子量: 40403.090 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: GNAI1 / 発現宿主: Insecta environmental sample (昆虫) / 参照: UniProt: P63096 |
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#3: タンパク質 | 分子量: 38744.371 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: GNB1 / 発現宿主: Insecta environmental sample (昆虫) / 参照: UniProt: P62873 |
#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 / 発現宿主: Insecta environmental sample (昆虫) / 参照: UniProt: P59768 |
-タンパク質 / 抗体 / タンパク質・ペプチド , 3種, 3分子 RSL
#1: タンパク質 | 分子量: 40667.375 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: SSTR4 / 発現宿主: Insecta environmental sample (昆虫) / 参照: UniProt: P31391 |
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#5: 抗体 | 分子量: 31549.107 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Mus musculus (ハツカネズミ) / 発現宿主: Insecta environmental sample (昆虫) |
#6: タンパク質・ペプチド | 分子量: 1641.909 Da / 分子数: 1 / 由来タイプ: 合成 / 由来: (合成) Homo sapiens (ヒト) / 参照: UniProt: P61278 |
-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: Complex structure of somatostatin receptor 4 (SSTR4) in complex with Gi and its endogeneous ligand SST-14 タイプ: COMPLEX / Entity ID: all / 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: Insecta environmental sample (昆虫) |
緩衝液 | pH: 7.5 |
試料 | 濃度: 1 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: NICKEL/TITANIUM |
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: 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 / 最大 デフォーカス(公称値): 2300 nm / 最小 デフォーカス(公称値): 1300 nm |
撮影 | 電子線照射量: 70 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 |
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CTF補正 | タイプ: NONE | ||||||||||||||||||||||||
3次元再構成 | 解像度: 2.9 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 799646 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
精密化 | 立体化学のターゲット値: GeoStd + Monomer Library + CDL v1.2 | ||||||||||||||||||||||||
拘束条件 |
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