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基本情報
登録情報 | データベース: PDB / ID: 7f2o | |||||||||||||||||||||
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タイトル | Cryo-EM structure of the type 2 bradykinin receptor in complex with the bradykinin and an Gq protein | |||||||||||||||||||||
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![]() | MEMBRANE PROTEIN / GPCR / Complex | |||||||||||||||||||||
機能・相同性 | ![]() negative regulation of intrinsic apoptotic signaling pathway in response to osmotic stress by p53 class mediator / bradykinin receptor activity / regulation of vascular permeability / phosphatidylinositol phospholipase C activity / vasoconstriction / 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 ...negative regulation of intrinsic apoptotic signaling pathway in response to osmotic stress by p53 class mediator / bradykinin receptor activity / regulation of vascular permeability / phosphatidylinositol phospholipase C activity / vasoconstriction / 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 / 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 / type 1 angiotensin receptor binding / Adrenaline,noradrenaline inhibits insulin secretion / ADP signalling through P2Y purinoceptor 12 / G alpha (q) signalling events / blood circulation / G alpha (i) signalling events / Thrombin signalling through proteinase activated receptors (PARs) / 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 / alkylglycerophosphoethanolamine phosphodiesterase activity / ADP signalling through P2Y purinoceptor 12 / 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 / arachidonic acid secretion / spectrin binding / Vasopressin regulates renal water homeostasis via Aquaporins / negative regulation of peptidyl-serine phosphorylation / plasma membrane => GO:0005886 / smooth muscle contraction / regulation of vasoconstriction / photoreceptor outer segment / cardiac muscle cell apoptotic process / cell surface receptor protein tyrosine kinase signaling pathway / response to salt stress / photoreceptor inner segment / Peptide ligand-binding receptors / G protein-coupled receptor activity / cellular response to catecholamine stimulus / sensory perception of taste / adenylate cyclase-activating dopamine receptor signaling pathway / vasodilation / cellular response to prostaglandin E stimulus / G-protein beta-subunit binding / heterotrimeric G-protein complex / signaling receptor complex adaptor activity / GTPase binding / retina development in camera-type eye / phospholipase C-activating G protein-coupled receptor signaling pathway / G alpha (i) signalling events / positive regulation of cytosolic calcium ion concentration / cell body / cellular response to hypoxia / G alpha (q) signalling events / protease binding / cell population proliferation / cell surface receptor signaling pathway / endosome / inflammatory response / G protein-coupled receptor signaling pathway / protein heterodimerization activity / intracellular membrane-bounded organelle / GTPase activity / dendrite / protein-containing complex binding / Golgi apparatus / membrane / plasma membrane / cytoplasm 類似検索 - 分子機能 | |||||||||||||||||||||
生物種 | ![]() ![]() ![]() synthetic construct (人工物) ![]() ![]() | |||||||||||||||||||||
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 | |||||||||||||||||||||
![]() | Yin, Y. / Jiang, Y. | |||||||||||||||||||||
資金援助 | ![]()
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![]() | ![]() 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. | |||||||||||||||||||||
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構造の表示
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構造ビューア | 分子: ![]() ![]() |
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PDBx/mmCIF形式 | ![]() | 221.1 KB | 表示 | ![]() |
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PDB形式 | ![]() | 173.1 KB | 表示 | ![]() |
PDBx/mmJSON形式 | ![]() | ツリー表示 | ![]() | |
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-検証レポート
文書・要旨 | ![]() | 712.9 KB | 表示 | ![]() |
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文書・詳細版 | ![]() | 720 KB | 表示 | |
XML形式データ | ![]() | 33.8 KB | 表示 | |
CIF形式データ | ![]() | 52.3 KB | 表示 | |
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-関連構造データ
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リンク
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集合体
登録構造単位 | ![]()
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要素
-タンパク質 , 2種, 2分子 AR
#1: 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) ![]() 発現宿主: ![]() ![]() |
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#4: タンパク質 | 分子量: 67152.914 Da / 分子数: 1 / Mutation: C146W / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() 発現宿主: ![]() ![]() 参照: UniProt: P30411 |
-Guanine nucleotide-binding protein ... , 2種, 2分子 BY
#2: 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) ![]() ![]() 発現宿主: ![]() ![]() 参照: UniProt: P54311 |
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#6: 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) ![]() ![]() 発現宿主: ![]() ![]() 参照: UniProt: P63212 |
-タンパク質・ペプチド / 抗体 , 2種, 2分子 DS
#3: タンパク質・ペプチド | 分子量: 1062.224 Da / 分子数: 1 / 由来タイプ: 合成 / 由来: (合成) ![]() |
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#5: 抗体 | 分子量: 26392.385 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) synthetic construct (人工物) 発現宿主: ![]() ![]() |
-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 |
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試料調製
構成要素 |
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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 |
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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: 80 e/Å2 / フィルム・検出器のモデル: OTHER |
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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: 2.9 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 664416 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
拘束条件 |
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