+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 7eib | |||||||||||||||||||||
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タイトル | Cryo-EM structure of the type 1 bradykinin receptor in complex with the des-Arg10-kallidin and an Gq protein | |||||||||||||||||||||
要素 |
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キーワード | MEMBRANE PROTEIN / Bradykinin receptors / Kinin / GPCR | |||||||||||||||||||||
機能・相同性 | 機能・相同性情報 bradykinin receptor 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 / Ca2+ pathway / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding ...bradykinin receptor 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 / Ca2+ pathway / 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 / : / 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 / positive regulation of leukocyte migration / 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 / plasma membrane => GO:0005886 / photoreceptor outer segment / response to mechanical stimulus / cardiac muscle cell apoptotic process / sensory perception of pain / negative regulation of blood pressure / photoreceptor inner segment / Peptide ligand-binding receptors / positive regulation of release of sequestered calcium ion into cytosol / negative regulation of protein phosphorylation / G protein-coupled receptor activity / peptide binding / negative regulation of cell growth / cellular response to catecholamine stimulus / sensory perception of taste / adenylate cyclase-activating dopamine receptor signaling pathway / cellular response to prostaglandin E stimulus / G-protein beta-subunit binding / heterotrimeric G-protein complex / cell migration / signaling receptor complex adaptor activity / GTPase binding / retina development in camera-type eye / phospholipase C-activating G protein-coupled receptor signaling pathway / positive regulation of cytosolic calcium ion concentration / G alpha (i) signalling events / cellular response to hypoxia / cell body / G alpha (q) signalling events / response to lipopolysaccharide / cell population proliferation / inflammatory response / neuron projection / G protein-coupled receptor signaling pathway / GTPase activity / dendrite / synapse / protein-containing complex binding / endoplasmic reticulum / membrane / plasma membrane / cytoplasm 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) | |||||||||||||||||||||
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 Å | |||||||||||||||||||||
データ登録者 | Yin, Y. / Jiang, Y. | |||||||||||||||||||||
資金援助 | 中国, 6件
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引用 | ジャーナル: Nat Struct Mol Biol / 年: 2021 タイトル: Molecular basis for kinin selectivity and activation of the human bradykinin receptors. 著者: Yu-Ling Yin / Chenyu Ye / Fulai Zhou / Jia Wang / Dehua Yang / Wanchao Yin / Ming-Wei Wang / H Eric Xu / Yi Jiang / 要旨: Bradykinin and kallidin are endogenous kinin peptide hormones that belong to the kallikrein-kinin system and are essential to the regulation of blood pressure, inflammation, coagulation and pain ...Bradykinin and kallidin are endogenous kinin peptide hormones that belong to the kallikrein-kinin system and are essential to the regulation of blood pressure, inflammation, coagulation and pain control. Des-Arg-kallidin, the carboxy-terminal des-Arg metabolite of kallidin, and bradykinin selectively activate two G protein-coupled receptors, type 1 and type 2 bradykinin receptors (B1R and B2R), respectively. The hyperactivation of bradykinin receptors, termed 'bradykinin storm', is associated with pulmonary edema in COVID-19 patients, suggesting that bradykinin receptors are important targets for COVID-19 intervention. Here we report two G protein-coupled complex structures of human B1R and B2R bound to des-Arg-kallidin and bradykinin, respectively. Combined with functional analysis, our structures reveal the mechanism of ligand selectivity and specific activation of the bradykinin receptor. These findings also provide a framework for guiding drug design targeting bradykinin receptors for the treatment of inflammation, cardiovascular disorders and COVID-19. | |||||||||||||||||||||
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 | 7eib.cif.gz | 183.7 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb7eib.ent.gz | 140 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 7eib.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 | 7eib_validation.pdf.gz | 706.1 KB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 7eib_full_validation.pdf.gz | 709.6 KB | 表示 | |
XML形式データ | 7eib_validation.xml.gz | 28.6 KB | 表示 | |
CIF形式データ | 7eib_validation.cif.gz | 43.7 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/ei/7eib ftp://data.pdbj.org/pub/pdb/validation_reports/ei/7eib | 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
#1: タンパク質 | 分子量: 69344.070 Da / 分子数: 1 / 変異: F126W / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: BDKRB1, BRADYB1 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) 参照: UniProt: P46663 |
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#2: タンパク質・ペプチド | 分子量: 1034.210 Da / 分子数: 1 / 由来タイプ: 合成 / 由来: (合成) Homo sapiens (ヒト) |
#3: タンパク質 | 分子量: 41724.383 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) |
#4: タンパク質 | 分子量: 41055.867 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: 7861.143 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 |
-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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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 | 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: FEI TITAN KRIOS |
電子銃 | 電子線源: OTHER / 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: 61.8 e/Å2 / フィルム・検出器のモデル: OTHER |
-解析
ソフトウェア | 名称: PHENIX / バージョン: 1.18.2_3874: / 分類: 精密化 | ||||||||||||||||||||||||
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CTF補正 | タイプ: NONE | ||||||||||||||||||||||||
3次元再構成 | 解像度: 3 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 633636 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
拘束条件 |
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