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基本情報
登録情報 | データベース: PDB / ID: 7f6h | |||||||||||||||||||||
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タイトル | Cryo-EM structure of human bradykinin receptor BK2R in complex Gq proteins and bradykinin | |||||||||||||||||||||
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![]() | MEMBRANE PROTEIN / GPCR / bradykinin receptor | |||||||||||||||||||||
機能・相同性 | ![]() Fatty Acids bound to GPR40 (FFAR1) regulate insulin secretion / Acetylcholine regulates insulin secretion / phospholipase C-activating G protein-coupled glutamate receptor signaling pathway / phospholipase C-activating serotonin receptor signaling pathway / PLC beta mediated events / entrainment of circadian clock / regulation of platelet activation / regulation of canonical Wnt signaling pathway / glutamate receptor signaling pathway / phototransduction, visible light ...Fatty Acids bound to GPR40 (FFAR1) regulate insulin secretion / Acetylcholine regulates insulin secretion / phospholipase C-activating G protein-coupled glutamate receptor signaling pathway / phospholipase C-activating serotonin receptor signaling pathway / PLC beta mediated events / entrainment of circadian clock / regulation of platelet activation / regulation of canonical Wnt signaling pathway / glutamate receptor signaling pathway / phototransduction, visible light / postsynaptic cytosol / photoreceptor outer segment / neuropeptide signaling pathway / enzyme regulator activity / response to prostaglandin E / GTPase activator activity / Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZO1 and integrins in endothelial cells / negative regulation of protein kinase activity / G protein-coupled receptor binding / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / Activation of the phototransduction cascade / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / G protein-coupled acetylcholine receptor signaling pathway / adenylate cyclase-activating G protein-coupled 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 / G beta:gamma signalling through CDC42 / Glucagon signaling in metabolic regulation / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / ADP signalling through P2Y purinoceptor 12 / Sensory perception of sweet, bitter, and umami (glutamate) taste / photoreceptor disc membrane / Glucagon-type ligand receptors / Adrenaline,noradrenaline inhibits insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / blood coagulation / G alpha (z) signalling events / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / cellular response to catecholamine stimulus / ADORA2B mediated anti-inflammatory cytokines production / ADP signalling through P2Y purinoceptor 1 / G beta:gamma signalling through PI3Kgamma / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / adenylate cyclase-activating dopamine receptor signaling pathway / GPER1 signaling / Inactivation, recovery and regulation of the phototransduction cascade / cellular response to prostaglandin E stimulus / G-protein beta-subunit binding / heterotrimeric G-protein complex / G alpha (12/13) signalling events / sensory perception of taste / extracellular vesicle / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / G protein activity / GTPase binding / Ca2+ pathway / retina development in camera-type eye / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / fibroblast proliferation / G alpha (i) signalling events / 加水分解酵素; 酸無水物に作用; GTPに作用・細胞または細胞小器官の運動に関与 / G alpha (s) signalling events / phospholipase C-activating G protein-coupled receptor signaling pathway / nuclear membrane / G alpha (q) signalling events / Ras protein signal transduction / Extra-nuclear estrogen signaling / cell population proliferation / protein stabilization / G protein-coupled receptor signaling pathway / lysosomal membrane / GTPase activity / synapse / protein-containing complex binding / GTP binding / Golgi apparatus / signal transduction / extracellular exosome / metal ion binding / membrane / plasma membrane / cytosol / cytoplasm 類似検索 - 分子機能 | |||||||||||||||||||||
生物種 | ![]() | |||||||||||||||||||||
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 | |||||||||||||||||||||
![]() | Shen, J. / Zhang, D. / Fu, Y. / Chen, A. / Zhang, H. | |||||||||||||||||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Cryo-EM structures of human bradykinin receptor-G proteins complexes. 著者: Jinkang Shen / Dongqi Zhang / Yao Fu / Anqi Chen / Xiaoli Yang / Haitao Zhang / ![]() 要旨: The type 2 bradykinin receptor (B2R) is a G protein-coupled receptor (GPCR) in the cardiovascular system, and the dysfunction of B2R leads to inflammation, hereditary angioedema, and pain. Bradykinin ...The type 2 bradykinin receptor (B2R) is a G protein-coupled receptor (GPCR) in the cardiovascular system, and the dysfunction of B2R leads to inflammation, hereditary angioedema, and pain. Bradykinin and kallidin are both endogenous peptide agonists of B2R, acting as vasodilators to protect the cardiovascular system. Here we determine two cryo-electron microscopy (cryo-EM) structures of human B2R-G in complex with bradykinin and kallidin at 3.0 Å and 2.9 Å resolution, respectively. The ligand-binding pocket accommodates S-shaped peptides, with aspartic acids and glutamates as an anion trap. The phenylalanines at the tail of the peptides induce significant conformational changes in the toggle switch W283, the conserved PIF, DRY, and NPxxY motifs, for the B2R activation. This further induces the extensive interactions of the intracellular loops ICL2/3 and helix 8 with G proteins. Our structures elucidate the molecular mechanisms for the ligand binding, receptor activation, and G proteins coupling of B2R. | |||||||||||||||||||||
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構造の表示
ムービー |
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構造ビューア | 分子: ![]() ![]() |
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PDBx/mmCIF形式 | ![]() | 191 KB | 表示 | ![]() |
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PDB形式 | ![]() | 139.5 KB | 表示 | ![]() |
PDBx/mmJSON形式 | ![]() | ツリー表示 | ![]() | |
その他 | ![]() |
-検証レポート
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
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-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
-Guanine nucleotide-binding protein ... , 3種, 3分子 BCD
#3: タンパク質 | 分子量: 43534.449 Da / 分子数: 1 / Mutation: R183Q, Q209L / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() 発現宿主: ![]() ![]() 参照: UniProt: P50148 |
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#4: タンパク質 | 分子量: 39086.641 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: P62873 |
#5: タンパク質 | 分子量: 9242.612 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: P59768 |
-タンパク質 / タンパク質・ペプチド / 非ポリマー , 3種, 4分子 AL

#1: タンパク質 | 分子量: 86464.734 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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#2: 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 詳細: This peptide is the ligand of the protein bradykinin receptor B2R 由来: (合成) ![]() |
#6: 化合物 |
-詳細
研究の焦点であるリガンドがあるか | N |
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Has protein modification | Y |
-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 | 名称: Bradykinin receptor BK2RR in complex with Gq proteins and bradykinin タイプ: COMPLEX / Entity ID: #1-#5 / 由来: RECOMBINANT |
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分子量 | 値: 0.173 MDa / 実験値: YES |
由来(天然) | 生物種: ![]() |
由来(組換発現) | 生物種: ![]() ![]() |
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: ![]() |
電子レンズ | モード: BRIGHT FIELD |
撮影 | 電子線照射量: 64 e/Å2 フィルム・検出器のモデル: GATAN K2 BASE (4k x 4k) |
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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: 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: 3960198 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
拘束条件 |
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