+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 7d3s | ||||||
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タイトル | Human SECR in complex with an engineered Gs heterotrimer | ||||||
要素 |
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キーワード | MEMBRANE PROTEIN / CLASS B GPCR / Secretin / SECR / SIGNALING PROTEIN-HORMONE COMPLEX | ||||||
機能・相同性 | 機能・相同性情報 secretin receptor activity / digestive hormone activity / positive regulation of somatostatin secretion / negative regulation of gastrin-induced gastric acid secretion / positive regulation of pancreatic juice secretion / regulation of appetite / pancreatic juice secretion / intracellular water homeostasis / positive regulation of lipid catabolic process / positive regulation of cAMP-mediated signaling ...secretin receptor activity / digestive hormone activity / positive regulation of somatostatin secretion / negative regulation of gastrin-induced gastric acid secretion / positive regulation of pancreatic juice secretion / regulation of appetite / pancreatic juice secretion / intracellular water homeostasis / positive regulation of lipid catabolic process / positive regulation of cAMP-mediated signaling / embryonic digestive tract development / 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 / G protein-coupled peptide receptor activity / 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 / Activation of G protein gated Potassium channels / G-protein activation / G beta:gamma signalling through PI3Kgamma / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through PLC beta / ADP signalling through P2Y purinoceptor 1 / Thromboxane signalling through TP receptor / Presynaptic function of Kainate receptors / G beta:gamma signalling through CDC42 / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / Glucagon-type ligand receptors / Adrenaline,noradrenaline inhibits insulin secretion / G alpha (12/13) signalling events / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / alkylglycerophosphoethanolamine phosphodiesterase activity / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / Thrombin signalling through proteinase activated receptors (PARs) / Ca2+ pathway / G alpha (z) signalling events / Extra-nuclear estrogen signaling / G alpha (s) signalling events / G alpha (q) signalling events / photoreceptor outer segment membrane / G alpha (i) signalling events / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / spectrin binding / Vasopressin regulates renal water homeostasis via Aquaporins / cytoplasmic microtubule / diet induced thermogenesis / 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 / cardiac muscle cell apoptotic process / adenylate cyclase activator activity / photoreceptor inner segment / response to nutrient levels / trans-Golgi network membrane / G protein-coupled receptor binding / hippocampus development / G-protein beta/gamma-subunit complex binding / bone development / brain development / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / regulation of synaptic plasticity / adenylate cyclase-activating G protein-coupled receptor signaling pathway / hormone activity / Prostacyclin signalling through prostacyclin receptor / Glucagon signaling in metabolic regulation / cognition / platelet aggregation / 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 / adenylate cyclase-activating dopamine receptor signaling pathway / cellular response to prostaglandin E stimulus / GPER1 signaling / G-protein beta-subunit binding 類似検索 - 分子機能 | ||||||
生物種 | Homo sapiens (ヒト) Rattus norvegicus (ドブネズミ) Bos taurus (ウシ) unidentified (未定義) | ||||||
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 | Fukuhara, S. / Kobayashi, K. / Kusakizako, T. / Shihoya, W. / Nureki, O. | ||||||
引用 | ジャーナル: Biochem Biophys Res Commun / 年: 2020 タイトル: Structure of the human secretin receptor coupled to an engineered heterotrimeric G protein. 著者: Satoshi Fukuhara / Kazuhiro Kobayashi / Tsukasa Kusakizako / Wataru Iida / Masahiko Kato / Wataru Shihoya / Osamu Nureki / 要旨: Secretin is a gastrointestinal hormone that exerts multiple physiological functions via activation of the secretin receptor (SECR). SECR belongs to the class B G-protein-coupled receptors and is ...Secretin is a gastrointestinal hormone that exerts multiple physiological functions via activation of the secretin receptor (SECR). SECR belongs to the class B G-protein-coupled receptors and is involved in various processes, such as regulation of the pH of the duodenal content, food intake, and water homeostasis. Here, we report a cryo-electron microscopy structure of human SECR bound to secretin and an engineered Gs heterotrimer. The structure revealed the basic architecture of SECR and the secretin binding mode. A structural comparison of the SECR and PAC1R transmembrane domains revealed that transmembrane helices 1 and 2 play a prominent role in secretin recognition. Moreover, the extracellular domain of SECR is perpendicular to the TMD, unlike that of PAC1R. This comparison revealed the diverged peptide recognition mechanisms of these receptors, which belong to the same subgroup. Our structural information will facilitate drug discovery research for clinical applications. | ||||||
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 | 7d3s.cif.gz | 198.7 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb7d3s.ent.gz | 158.1 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 7d3s.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 | 7d3s_validation.pdf.gz | 1004.5 KB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 7d3s_full_validation.pdf.gz | 1017.1 KB | 表示 | |
XML形式データ | 7d3s_validation.xml.gz | 40.7 KB | 表示 | |
CIF形式データ | 7d3s_validation.cif.gz | 61.7 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/d3/7d3s ftp://data.pdbj.org/pub/pdb/validation_reports/d3/7d3s | 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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-要素
-Guanine nucleotide-binding protein ... , 3種, 3分子 ABG
#3: タンパク質 | 分子量: 44255.664 Da / 分子数: 1 Mutation: deletion 254-263, G49D,E50N,L63Y,A249D,S252D,I375A,V375I 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: Escherichia coli (大腸菌) / 参照: UniProt: P63092 |
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#4: 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) Rattus norvegicus (ドブネズミ) / 遺伝子: Gnb1 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) 参照: UniProt: P54311 |
#5: タンパク質 | 分子量: 7547.685 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Bos taurus (ウシ) / 遺伝子: GNG2 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) 参照: UniProt: P63212 |
-タンパク質・ペプチド / タンパク質 / 抗体 , 3種, 3分子 PRN
#1: タンパク質・ペプチド | 分子量: 3045.436 Da / 分子数: 1 / 由来タイプ: 合成 / 由来: (合成) Homo sapiens (ヒト) / 参照: UniProt: P09683 |
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#2: タンパク質 | 分子量: 49742.422 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: SCTR 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) 参照: UniProt: P47872 |
#6: 抗体 | 分子量: 15015.728 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) unidentified (未定義) / 発現宿主: Escherichia coli (大腸菌) |
-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 | 実験値: NO | ||||||||||||||||||||||||||||||||||||||||||||||||
由来(天然) | 生物種: Homo sapiens (ヒト) | ||||||||||||||||||||||||||||||||||||||||||||||||
由来(組換発現) |
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緩衝液 | pH: 8 | ||||||||||||||||||||||||||||||||||||||||||||||||
試料 | 濃度: 5.4 mg/ml / 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES | ||||||||||||||||||||||||||||||||||||||||||||||||
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 |
-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: OTHER |
電子レンズ | モード: BRIGHT FIELD |
撮影 | 電子線照射量: 50.8 e/Å2 / フィルム・検出器のモデル: GATAN K3 (6k x 4k) / 実像数: 2142 |
-解析
EMソフトウェア | 名称: PHENIX / バージョン: 1.14 / カテゴリ: モデル精密化 / 詳細: phenix.real_space_refine |
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CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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: 617465 / 対称性のタイプ: POINT |
原子モデル構築 | プロトコル: OTHER |
原子モデル構築 | PDB-ID: 5VAI |