+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 7p02 | |||||||||
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タイトル | Human Neurokinin 1 receptor (NK1R) substance P Gs complex | |||||||||
要素 |
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キーワード | MEMBRANE PROTEIN / Receptor / Complex / Eukaryotic protein | |||||||||
機能・相同性 | 機能・相同性情報 substance P receptor binding / substance P receptor activity / tachykinin receptor activity / positive regulation of flagellated sperm motility / insemination / aggressive behavior / Tachykinin receptors bind tachykinins / positive regulation of uterine smooth muscle contraction / positive regulation of synaptic transmission, cholinergic / detection of abiotic stimulus ...substance P receptor binding / substance P receptor activity / tachykinin receptor activity / positive regulation of flagellated sperm motility / insemination / aggressive behavior / Tachykinin receptors bind tachykinins / positive regulation of uterine smooth muscle contraction / positive regulation of synaptic transmission, cholinergic / detection of abiotic stimulus / tachykinin receptor signaling pathway / operant conditioning / positive regulation of lymphocyte proliferation / sperm head / response to ozone / sperm ejaculation / positive regulation of action potential / response to auditory stimulus / regulation of smooth muscle cell proliferation / smooth muscle contraction involved in micturition / positive regulation of blood pressure / positive regulation of hormone secretion / positive regulation of vascular permeability / positive regulation of ossification / regulation of smooth muscle cell migration / positive regulation of leukocyte migration / eating behavior / response to pain / positive regulation of epithelial cell migration / behavioral response to pain / associative learning / angiotensin-mediated drinking behavior / neuropeptide signaling pathway / sperm flagellum / T cell migration / D2 dopamine receptor binding / Adenylate cyclase inhibitory pathway / positive regulation of protein localization to cell cortex / regulation of cAMP-mediated signaling / response to electrical stimulus / long-term memory / G protein-coupled serotonin receptor binding / cellular response to forskolin / positive regulation of vasoconstriction / regulation of mitotic spindle organization / sperm midpiece / positive regulation of stress fiber assembly / sensory perception of pain / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / G-protein beta/gamma-subunit complex binding / positive regulation of epithelial cell proliferation / cellular response to nerve growth factor stimulus / response to progesterone / Regulation of insulin secretion / positive regulation of synaptic transmission, GABAergic / G protein-coupled receptor binding / response to nicotine / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / Olfactory Signaling Pathway / Activation of the phototransduction cascade / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / Glucagon signaling in metabolic regulation / G protein-coupled acetylcholine receptor signaling pathway / G-protein activation / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / G beta:gamma signalling through CDC42 / response to peptide hormone / Vasopressin regulates renal water homeostasis via Aquaporins / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / Glucagon-type ligand receptors / Sensory perception of sweet, bitter, and umami (glutamate) taste / photoreceptor disc membrane / G alpha (z) signalling events / Adrenaline,noradrenaline inhibits insulin secretion / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / ADORA2B mediated anti-inflammatory cytokines production / cellular response to catecholamine stimulus / sensory perception of taste / ADP signalling through P2Y purinoceptor 1 / adenylate cyclase-activating dopamine receptor signaling pathway / G beta:gamma signalling through PI3Kgamma / GPER1 signaling / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / GDP binding / cellular response to prostaglandin E stimulus / Inactivation, recovery and regulation of the phototransduction cascade / G-protein beta-subunit binding / heterotrimeric G-protein complex / G alpha (12/13) signalling events / extracellular vesicle / Cargo recognition for clathrin-mediated endocytosis / signaling receptor complex adaptor activity / 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 / Thrombin signalling through proteinase activated receptors (PARs) 類似検索 - 分子機能 | |||||||||
生物種 | Mus musculus (ハツカネズミ) Homo sapiens (ヒト) | |||||||||
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: 2.87 Å | |||||||||
データ登録者 | Thom, C. / Ehrenmann, J. / Vacca, S. / Waltenspuhl, Y. / Schoppe, J. / Medalia, O. / Pluckthun, A. | |||||||||
資金援助 | スイス, 2件
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引用 | ジャーナル: Sci Adv / 年: 2021 タイトル: Structures of neurokinin 1 receptor in complex with G and G proteins reveal substance P binding mode and unique activation features. 著者: Cristian Thom / Janosch Ehrenmann / Santiago Vacca / Yann Waltenspühl / Jendrik Schöppe / Ohad Medalia / Andreas Plückthun / 要旨: The neurokinin 1 receptor (NKR) is involved in inflammation and pain transmission. This pathophysiologically important G protein–coupled receptor is predominantly activated by its cognate agonist ...The neurokinin 1 receptor (NKR) is involved in inflammation and pain transmission. This pathophysiologically important G protein–coupled receptor is predominantly activated by its cognate agonist substance P (SP) but also by the closely related neurokinins A and B. Here, we report cryo–electron microscopy structures of SP-bound NKR in complex with its primary downstream signal mediators, G and G. Our structures reveal how a polar network at the extracellular, solvent-exposed receptor surface shapes the orthosteric pocket and that NKR adopts a noncanonical active-state conformation with an interface for G protein binding, which is distinct from previously reported structures. Detailed comparisons with antagonist-bound NKR crystal structures reveal that insurmountable antagonists induce a distinct and long-lasting receptor conformation that sterically blocks SP binding. Together, our structures provide important structural insights into ligand and G protein promiscuity, the lack of basal signaling, and agonist- and antagonist-induced conformations in the neurokinin receptor family. | |||||||||
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 | 7p02.cif.gz | 214.1 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb7p02.ent.gz | 171.7 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 7p02.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 | 7p02_validation.pdf.gz | 644.2 KB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 7p02_full_validation.pdf.gz | 652.3 KB | 表示 | |
XML形式データ | 7p02_validation.xml.gz | 33 KB | 表示 | |
CIF形式データ | 7p02_validation.cif.gz | 46.8 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/p0/7p02 ftp://data.pdbj.org/pub/pdb/validation_reports/p0/7p02 | 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
-Guanine nucleotide-binding protein ... , 3種, 3分子 BGA
#2: 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) Homo sapiens (ヒト) / 遺伝子: GNB1 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) 参照: UniProt: P62873 |
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#3: 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: Spodoptera frugiperda (ツマジロクサヨトウ) 参照: UniProt: P59768 |
#4: タンパク質 | 分子量: 28428.365 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, GNAS, GNAS1, GSP 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) 参照: UniProt: P63096, UniProt: P63092 |
-抗体 / タンパク質 / タンパク質・ペプチド / 非ポリマー , 4種, 4分子 HRP
#1: 抗体 | 分子量: 32409.229 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: Spodoptera frugiperda (ツマジロクサヨトウ) |
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#5: タンパク質 | 分子量: 44218.668 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: TACR1, NK1R, TAC1R 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) 参照: UniProt: P25103 |
#6: タンパク質・ペプチド | 分子量: 1348.637 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: TAC1, NKA, NKNA, TAC2 発現宿主: Spodoptera frugiperda (ツマジロクサヨトウ) 参照: UniProt: P20366 |
#7: 化合物 | ChemComp-CLR / |
-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 |
-試料調製
構成要素 | 名称: NK1R in complex with Substance P, heterotrimeric mini-Gs chimera (Gsi) and scFv16 タイプ: COMPLEX / Entity ID: #1-#6 / 由来: RECOMBINANT |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
由来(組換発現) | 生物種: Spodoptera frugiperda (ツマジロクサヨトウ) |
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: GOLD / グリッドのタイプ: Quantifoil R1.2/1.3 |
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: FLOOD BEAM |
電子レンズ | モード: BRIGHT FIELD / 倍率(公称値): 130000 X / 最大 デフォーカス(公称値): 2400 nm / Calibrated defocus min: 800 nm / Cs: 2.7 mm |
試料ホルダ | 凍結剤: NITROGEN |
撮影 | 電子線照射量: 63.51 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 | 名称: PHENIX / バージョン: 1.19.1_4122: / 分類: 精密化 | ||||||||||||||||||||||||
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EMソフトウェア |
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CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
粒子像の選択 | 選択した粒子像数: 4227825 | ||||||||||||||||||||||||
3次元再構成 | 解像度: 2.87 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 395052 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
拘束条件 |
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