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基本情報
登録情報 | データベース: EMDB / ID: EMD-13140 | |||||||||
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タイトル | Human Neurokinin 1 receptor (NK1R) substance P Gq chimera (mGsqi) complex | |||||||||
![]() | processed map | |||||||||
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![]() | Receptor / Complex / Eukaryotic protein / Membrane protein | |||||||||
機能・相同性 | ![]() substance P receptor activity / tachykinin receptor activity / positive regulation of flagellated sperm motility / aggressive behavior / Tachykinin receptors bind tachykinins / sperm ejaculation / positive regulation of uterine smooth muscle contraction / positive regulation of synaptic transmission, cholinergic / detection of abiotic stimulus / operant conditioning ...substance P receptor activity / tachykinin receptor activity / positive regulation of flagellated sperm motility / aggressive behavior / Tachykinin receptors bind tachykinins / sperm ejaculation / positive regulation of uterine smooth muscle contraction / positive regulation of synaptic transmission, cholinergic / detection of abiotic stimulus / operant conditioning / positive regulation of lymphocyte proliferation / tachykinin receptor signaling pathway / response to ozone / sperm head / response to auditory stimulus / positive regulation of action potential / positive regulation of hormone secretion / smooth muscle contraction involved in micturition / regulation of smooth muscle cell proliferation / positive regulation of blood pressure / positive regulation of vascular permeability / positive regulation of ossification / regulation of smooth muscle cell migration / positive regulation of leukocyte migration / eating behavior / associative learning / behavioral response to pain / angiotensin-mediated drinking behavior / sperm flagellum / positive regulation of epithelial cell migration / long-term memory / response to electrical stimulus / positive regulation of protein localization to cell cortex / Adenylate cyclase inhibitory pathway / T cell migration / D2 dopamine receptor binding / response to prostaglandin E / positive regulation of stress fiber assembly / G protein-coupled serotonin receptor binding / adenylate cyclase regulator activity / adenylate cyclase-inhibiting serotonin receptor signaling pathway / positive regulation of vasoconstriction / sperm midpiece / cellular response to forskolin / regulation of mitotic spindle organization / response to progesterone / positive regulation of epithelial cell proliferation / positive regulation of synaptic transmission, GABAergic / Regulation of insulin secretion / response to nicotine / positive regulation of cholesterol biosynthetic process / G protein-coupled receptor binding / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / G-protein beta/gamma-subunit complex binding / response to peptide hormone / centriolar satellite / 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 / 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 / GDP binding / 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 / Cargo recognition for clathrin-mediated endocytosis / sensory perception of taste / response to estradiol / extracellular vesicle / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / Clathrin-mediated endocytosis / G protein activity 類似検索 - 分子機能 | |||||||||
生物種 | ![]() ![]() ![]() | |||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 2.71 Å | |||||||||
![]() | Thom C / Ehrenmann J | |||||||||
資金援助 | ![]()
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![]() | ![]() 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
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構造ビューア | EMマップ: ![]() ![]() ![]() |
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画像 | ![]() | 47.4 KB | ||
Filedesc metadata | ![]() | 7.1 KB | ||
その他 | ![]() | 135.3 MB | ||
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文書・要旨 | ![]() | 495.3 KB | 表示 | ![]() |
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文書・詳細版 | ![]() | 494.9 KB | 表示 | |
XML形式データ | ![]() | 7.3 KB | 表示 | |
CIF形式データ | ![]() | 8.5 KB | 表示 | |
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「今月の分子」の関連する項目 |
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マップ
ファイル | ![]() | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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注釈 | processed map | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
投影像・断面図 | 画像のコントロール
画像は Spider により作成 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 0.651 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
CCP4マップ ヘッダ情報:
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-添付データ
-追加マップ: raw map
ファイル | emd_13140_additional_1.map | ||||||||||||
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注釈 | raw map | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
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試料の構成要素
-全体 : NK1R in complex with Substance P, heterotrimeric mini-Gq chimera ...
全体 | 名称: NK1R in complex with Substance P, heterotrimeric mini-Gq chimera (Gsqi) and scFv16 |
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要素 |
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-超分子 #1: NK1R in complex with Substance P, heterotrimeric mini-Gq chimera ...
超分子 | 名称: NK1R in complex with Substance P, heterotrimeric mini-Gq chimera (Gsqi) and scFv16 タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1-#6 |
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由来(天然) | 生物種: ![]() |
-分子 #1: Antibody fragment scFv16
分子 | 名称: Antibody fragment scFv16 / タイプ: protein_or_peptide / ID: 1 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() ![]() |
分子量 | 理論値: 32.409229 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: MKFLVNVALV FMVVYISYIY ADYKDDDDKH HHHHHHHHHL EVLFQGPDVQ LVESGGGLVQ PGGSRKLSCS ASGFAFSSFG MHWVRQAPE KGLEWVAYIS SGSGTIYYAD TVKGRFTISR DDPKNTLFLQ MTSLRSEDTA MYYCVRSIYY YGSSPFDFWG Q GTTLTVSS ...文字列: MKFLVNVALV FMVVYISYIY ADYKDDDDKH HHHHHHHHHL EVLFQGPDVQ LVESGGGLVQ PGGSRKLSCS ASGFAFSSFG MHWVRQAPE KGLEWVAYIS SGSGTIYYAD TVKGRFTISR DDPKNTLFLQ MTSLRSEDTA MYYCVRSIYY YGSSPFDFWG Q GTTLTVSS GGGGSGGGGS GGGGSDIVMT QATSSVPVTP GESVSISCRS SKSLLHSNGN TYLYWFLQRP GQSPQLLIYR MS NLASGVP DRFSGSGSGT AFTLTISRLE AEDVGVYYCM QHLEYPLTFG AGTKLELKAA A |
-分子 #2: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
分子 | 名称: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 タイプ: protein_or_peptide / ID: 2 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 39.086641 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: MHHHHHHHHH HGSSGSELDQ LRQEAEQLKN QIRDARKACA DATLSQITNN IDPVGRIQMR TRRTLRGHLA KIYAMHWGTD SRLLVSASQ DGKLIIWDSY TTNKVHAIPL RSSWVMTCAY APSGNYVACG GLDNICSIYN LKTREGNVRV SRELAGHTGY L SCCRFLDD ...文字列: MHHHHHHHHH HGSSGSELDQ LRQEAEQLKN QIRDARKACA DATLSQITNN IDPVGRIQMR TRRTLRGHLA KIYAMHWGTD SRLLVSASQ DGKLIIWDSY TTNKVHAIPL RSSWVMTCAY APSGNYVACG GLDNICSIYN LKTREGNVRV SRELAGHTGY L SCCRFLDD NQIVTSSGDT TCALWDIETG QQTTTFTGHT GDVMSLSLAP DTRLFVSGAC DASAKLWDVR EGMCRQTFTG HE SDINAIC FFPNGNAFAT GSDDATCRLF DLRADQELMT YSHDNIICGI TSVSFSKSGR LLLAGYDDFN CNVWDALKAD RAG VLAGHD NRVSCLGVTD DGMAVATGSW DSFLKIWN UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 |
-分子 #3: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
分子 | 名称: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 タイプ: protein_or_peptide / ID: 3 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 7.861143 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: MASNNTASIA QARKLVEQLK MEANIDRIKV SKAAADLMAY CEAHAKEDPL LTPVPASENP FREKKFFCAI L UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 |
-分子 #4: Guanine nucleotide-binding protein G(i) subunit alpha-1,Guanine n...
分子 | 名称: Guanine nucleotide-binding protein G(i) subunit alpha-1,Guanine nucleotide-binding protein G(s) subunit alpha isoforms short タイプ: protein_or_peptide / ID: 4 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 28.304219 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: MGCTLSAEDK AAVERSKMIE KQLQKDKQVY RATHRLLLLG ADNSGKSTIV KQMRILHGGS GGSGGTSGIF ETKFQVDKVN FHMFDVGGQ RDERRKWIQC FNDVTAIIFV VDSSDYNRLQ EALNLFKSIW NNRWLRTISV ILFLNKQDLL AEKVLAGKSK I EDYFPEFA ...文字列: MGCTLSAEDK AAVERSKMIE KQLQKDKQVY RATHRLLLLG ADNSGKSTIV KQMRILHGGS GGSGGTSGIF ETKFQVDKVN FHMFDVGGQ RDERRKWIQC FNDVTAIIFV VDSSDYNRLQ EALNLFKSIW NNRWLRTISV ILFLNKQDLL AEKVLAGKSK I EDYFPEFA RYTTPEDATP EPGEDPRVTR AKYFIRDEFL RISTASGDGR HYCYPHFTCA VDTENARRIF NDCKDIILQM NL REYNLV UniProtKB: Guanine nucleotide-binding protein G(i) subunit alpha-1, Guanine nucleotide-binding protein G(s) subunit alpha |
-分子 #5: Substance-P receptor
分子 | 名称: Substance-P receptor / タイプ: protein_or_peptide / ID: 5 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 44.218668 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: MKFLVNVALV FMVVYISYIY ADYKDDDDKH HHHHHHHHHL EVLFQGPMDN VLPVDSDLSP NISTNTSEPN QFVQPAWQIV LWAAAYTVI VVTSVVGNVV VMWIILAHKR MRTVTNYFLV NLAFAEASMA AFNTVVNFTY AVHNEWYYGL FYCKFHNFFP I AAVFASIY ...文字列: MKFLVNVALV FMVVYISYIY ADYKDDDDKH HHHHHHHHHL EVLFQGPMDN VLPVDSDLSP NISTNTSEPN QFVQPAWQIV LWAAAYTVI VVTSVVGNVV VMWIILAHKR MRTVTNYFLV NLAFAEASMA AFNTVVNFTY AVHNEWYYGL FYCKFHNFFP I AAVFASIY SMTAVAFDRY MAIIHPLQPR LSATATKVVI CVIWVLALLL AFPQGYYSTT ETMPSRVVCM IEWPEHPNKI YE KVYHICV TVLIYFLPLL VIGYAYTVVG ITLWASEIPG DSSDRYHEQV SAKRKVVKMM IVVVCTFAIC WLPFHIFFLL PYI NPDLYL KKFIQQVYLA IMWLAMSSTM YNPIIYCCLN DRFRLGFKHA FRCCPFISAG DYEGLE UniProtKB: Substance-P receptor |
-分子 #6: Substance P
分子 | 名称: Substance P / タイプ: protein_or_peptide / ID: 6 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 1.348637 KDa |
配列 | 文字列: RPKPQQFFGL M(NH2) |
-分子 #7: CHOLESTEROL
分子 | 名称: CHOLESTEROL / タイプ: ligand / ID: 7 / コピー数: 1 / 式: CLR |
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分子量 | 理論値: 386.654 Da |
Chemical component information | ![]() ChemComp-CLR: |
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
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![]() | 単粒子再構成法 |
試料の集合状態 | particle |
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試料調製
濃度 | 1 mg/mL |
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緩衝液 | pH: 7.5 |
グリッド | モデル: Quantifoil R1.2/1.3 / 材質: GOLD / 支持フィルム - 材質: CARBON / 支持フィルム - トポロジー: HOLEY |
凍結 | 凍結剤: ETHANE / チャンバー内湿度: 100 % / チャンバー内温度: 277 K / 装置: FEI VITROBOT MARK IV |
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電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
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撮影 | フィルム・検出器のモデル: GATAN K3 BIOQUANTUM (6k x 4k) 平均電子線量: 62.51 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: ![]() |
電子光学系 | 最小 デフォーカス(補正後): 0.8 µm / 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELD / Cs: 2.7 mm / 最大 デフォーカス(公称値): 2.4 µm / 倍率(公称値): 130000 |
試料ステージ | ホルダー冷却材: NITROGEN |
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |