+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-36145 | |||||||||
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タイトル | Neurokinin B bound to active human neurokinin 3 receptor in complex with Gq | |||||||||
マップデータ | Neurokinin B bound to active human neurokinin 3 receptor in complex with Gq | |||||||||
試料 |
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キーワード | G protein coupled receptor / Neurokinin / Cryo-EM / Peptide Agonists / MEMBRANE PROTEIN | |||||||||
機能・相同性 | 機能・相同性情報 Tachykinin receptors bind tachykinins / tachykinin receptor signaling pathway / positive regulation of blood pressure / 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 ...Tachykinin receptors bind tachykinins / tachykinin receptor signaling pathway / positive regulation of blood pressure / 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 / Adrenaline,noradrenaline inhibits insulin secretion / ADP signalling through P2Y purinoceptor 12 / G alpha (q) 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 / G alpha (i) signalling events / G alpha (12/13) signalling events / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / Adrenaline,noradrenaline inhibits insulin secretion / alkylglycerophosphoethanolamine phosphodiesterase activity / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / Thrombin signalling through proteinase activated receptors (PARs) / Ca2+ pathway / Extra-nuclear estrogen signaling / G alpha (z) signalling events / 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 / photoreceptor outer segment / neuropeptide signaling pathway / cardiac muscle cell apoptotic process / photoreceptor inner segment / female pregnancy / 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 / 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 / cellular response to hypoxia / cell body / G alpha (q) signalling events / cell population proliferation / G protein-coupled receptor signaling pathway / signaling receptor binding / GTPase activity / dendrite / synapse / protein-containing complex binding / extracellular space / extracellular region / 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) / Mus musculus (ハツカネズミ) / Bos taurus (ウシ) | |||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 2.8 Å | |||||||||
データ登録者 | Sun WJ / Yang F / Zhang HH / Yuan QN / Yin WC / Shi P / Eric X / Tian CL | |||||||||
資金援助 | 中国, 1件
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引用 | ジャーナル: Cell Discov / 年: 2023 タイトル: Structural insights into neurokinin 3 receptor activation by endogenous and analogue peptide agonists. 著者: Wenjing Sun / Fan Yang / Huanhuan Zhang / Qingning Yuan / Shenglong Ling / Yuanxia Wang / Pei Lv / Zelin Li / Yifan Luo / Dongsheng Liu / Wanchao Yin / Pan Shi / H Eric Xu / Changlin Tian / 要旨: Neurokinin 3 receptor (NK3R) is a tachykinin receptor essential for the hypothalamic-pituitary-gonadal axis. The endogenous peptide agonist neurokinin B (NKB) preferentially activates NK3R, while ...Neurokinin 3 receptor (NK3R) is a tachykinin receptor essential for the hypothalamic-pituitary-gonadal axis. The endogenous peptide agonist neurokinin B (NKB) preferentially activates NK3R, while substance P (SP) binds preferentially to NK1R. In addition, the SP analogue senktide more potently activates NK3R than NKB and SP. However, the mechanisms of preferential binding of peptide and NK3R activation remain elusive. Herein, we determined the cryogenic electron microscopy (cryo-EM) structures of the NK3R-G complex bound to NKB, SP and senktide. The three NK3R-G/peptide complexes utilize a class of noncanonical receptor activation mechanisms. Combining the structural analysis and functional assay illustrated that the consensus C-termini of the three peptide agonists share a conserved binding mode to NK3R, while the divergent N-termini of the peptides confer the preferential binding of the agonist to NK3R. In addition, the specific interactions between the N-terminus of senktide and the N-terminus and extracellular loops (ECL2 and ECL3) of NK3R lead to the improved activation displayed by senktide compared to SP and NKB. These findings pave the way to understand tachykinin receptor subtype selectivity and provide ideas to rationally develop drugs targeting NK3R. | |||||||||
履歴 |
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-構造の表示
添付画像 |
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-ダウンロードとリンク
-EMDBアーカイブ
マップデータ | emd_36145.map.gz | 28.7 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-36145-v30.xml emd-36145.xml | 21.6 KB 21.6 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_36145.png | 159.6 KB | ||
Filedesc metadata | emd-36145.cif.gz | 7.1 KB | ||
その他 | emd_36145_half_map_1.map.gz emd_36145_half_map_2.map.gz | 28.2 MB 28.2 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-36145 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-36145 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_36145_validation.pdf.gz | 773.1 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_36145_full_validation.pdf.gz | 772.7 KB | 表示 | |
XML形式データ | emd_36145_validation.xml.gz | 10.8 KB | 表示 | |
CIF形式データ | emd_36145_validation.cif.gz | 12.5 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-36145 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-36145 | HTTPS FTP |
-関連構造データ
-リンク
EMDBのページ | EMDB (EBI/PDBe) / EMDataResource |
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「今月の分子」の関連する項目 |
-マップ
ファイル | ダウンロード / ファイル: emd_36145.map.gz / 形式: CCP4 / 大きさ: 30.5 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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注釈 | Neurokinin B bound to active human neurokinin 3 receptor in complex with Gq | ||||||||||||||||||||||||||||||||||||
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: 1.07 Å | ||||||||||||||||||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
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-添付データ
-ハーフマップ: Neurokinin B bound to active human neurokinin 3...
ファイル | emd_36145_half_map_1.map | ||||||||||||
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注釈 | Neurokinin B bound to active human neurokinin 3 receptor in complex with Gq | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: Neurokinin B bound to active human neurokinin 3...
ファイル | emd_36145_half_map_2.map | ||||||||||||
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注釈 | Neurokinin B bound to active human neurokinin 3 receptor in complex with Gq | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-試料の構成要素
-全体 : Neurokinin B bound to active human neurokinin 3 receptor in compl...
全体 | 名称: Neurokinin B bound to active human neurokinin 3 receptor in complex with Gq heterotrimer |
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要素 |
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-超分子 #1: Neurokinin B bound to active human neurokinin 3 receptor in compl...
超分子 | 名称: Neurokinin B bound to active human neurokinin 3 receptor in complex with Gq heterotrimer タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: all |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
-分子 #1: Neuromedin-K receptor (NK3R-pFastbac1)
分子 | 名称: Neuromedin-K receptor (NK3R-pFastbac1) / 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: Homo sapiens (ヒト) |
分子量 | 理論値: 158.089531 KDa |
組換発現 | 生物種: Spodoptera frugiperda (ツマジロクサヨトウ) |
配列 | 文字列: MKTIIALSYI FCLVFAADLE DNWETLNDNL KVIEKADNAA QVKDALTKMR AAALDAQKAT PPKLEDKSPD SPEMKDFRHG FDILVGQID DALKLANEGK VKEAQAAAEQ LKTTRNAYIQ KYLMATLPAA ETWIDGGGGV GADAVNLTAS LAAGAATGAV E TGWLQLLD ...文字列: MKTIIALSYI FCLVFAADLE DNWETLNDNL KVIEKADNAA QVKDALTKMR AAALDAQKAT PPKLEDKSPD SPEMKDFRHG FDILVGQID DALKLANEGK VKEAQAAAEQ LKTTRNAYIQ KYLMATLPAA ETWIDGGGGV GADAVNLTAS LAAGAATGAV E TGWLQLLD QAGNLSSSPS ALGLPVASPA PSQPWANLTN QFVQPSWRIA LWSLAYGVVV AVAVLGNLIV IWIILAHKRM RT VTNYFLV NLAFSDASMA AFNTLVNFIY ALHSEWYFGA NYCRFQNFFP ITAVFASIYS MTAIAVDRYM AIIDPLKPRL SAT ATKIVI GSIWILAFLL AFPQCLYSKT KVMPGRTLCF VQWPEGPKQH FTYHIIVIIL VYCFPLLIMG ITYTIVGITL WGGE IPGDT CDKYHEQLKA KRKVVKMMII VVMTFAICWL PYHIYFILTA IYQQLNRWKY IQQVYLASFW LAMSSTMYNP IIYCC LNKR FRAGFKRAFR WCPFIKVSSY DELELKTTRF HPVFTLEDFV GDWEQTAAYN LDQVLEQGGV SSLLQNLAVS VTPIQR IVR SGENALKIDI HVIIPYEGLS ADQMAQIEEV FKVVYPVDDH HFKVILPYGT LVIDGVTPNM LNYFGRPYEG IAVFDGK KI TVTGTLWNGN KIIDERLITP DGSMLFRVTI NSGGSENLYF QGGSAGSAAK IEEGKLVIWI NGDKGYNGLA EVGKKFEK D TGIKVTVEHP DKLEEKFPQV AATGDGPDII FWAHDRFGGY AQSGLLAEIT PDKAFQDKLY PFTWDAVRYN GKLIAYPIA VEALSLIYNK DLLPNPPKTW EEIPALDKEL KAKGKSALMF NLQEPYFTWP LIAADGGYAF KYENGKYDIK DVGVDNAGAK AGLTFLVDL IKNKHMNADT DYSIAEAAFN KGETAMTING PWAWSNIDTS KVNYGVTVLP TFKGQPSKPF VGVLSAGINA A SPNKELAK EFLENYLLTD EGLEAVNKDK PLGAVALKSY EEELAKDPRI AATMENAQKG EIMPNIPQMS AFWYAVRTAV IN AASGRQT VDEALKDAQT AKIEEGKLVI WINGDKGYNG LAEVGKKFEK DTGIKVTVEH PDKLEEKFPQ VAATGDGPDI IFW AHDRFG GYAQSGLLAE ITPDKAFQDK LYPFTWDAVR YNGKLIAYPI AVEALSLIYN KDLLPNPPKT WEEIPALDKE LKAK GKSAL MFNLQEPYFT WPLIAADGGY AFKYENGKYD IKDVGVDNAG AKAGLTFLVD LIKNKHMNAD TDYSIAEAAF NKGET AMTI NGPWAWSNID TSKVNYGVTV LPTFKGQPSK PFVGVLSAGI NAASPNKELA KEFLENYLLT DEGLEAVNKD KPLGAV ALK SYEEELAKDP RIAATMENAQ KGEIMPNIPQ MSAFWYAVRT AVINAASGRQ TVDEALKDAQ TRITK |
-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: Rattus norvegicus (ドブネズミ) |
分子量 | 理論値: 41.055867 KDa |
組換発現 | 生物種: Spodoptera frugiperda (ツマジロクサヨトウ) |
配列 | 文字列: HMHHHHHGSL LQSELDQLRQ EAEQLKNQIR DARKACADAT LSQITNNIDP VGRIQMRTRR TLRGHLAKIY AMHWGTDSRL LVSASQDGK LIIWDSYTTN KVHAIPLRSS WVMTCAYAPS GNYVACGGLD NICSIYNLKT REGNVRVSRE LAGHTGYLSC C RFLDDNQI ...文字列: HMHHHHHGSL LQSELDQLRQ EAEQLKNQIR DARKACADAT LSQITNNIDP VGRIQMRTRR TLRGHLAKIY AMHWGTDSRL LVSASQDGK LIIWDSYTTN KVHAIPLRSS WVMTCAYAPS GNYVACGGLD NICSIYNLKT REGNVRVSRE LAGHTGYLSC C RFLDDNQI VTSSGDTTCA LWDIETGQQT TTFTGHTGDV MSLSLAPDTR LFVSGACDAS AKLWDVREGM CRQTFTGHES DI NAICFFP NGNAFATGSD DATCRLFDLR ADQELMTYSH DNIICGITSV SFSKSGRLLL AGYDDFNCNV WDALKADRAG VLA GHDNRV SCLGVTDDGM AVATGSWDSF LKIWNGSSGG GGSGGGGSSG VSGWRLFKKI S UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 |
-分子 #3: ScFv16 nanobody
分子 | 名称: ScFv16 nanobody / 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: Mus musculus (ハツカネズミ) |
分子量 | 理論値: 32.708473 KDa |
組換発現 | 生物種: Spodoptera frugiperda (ツマジロクサヨトウ) |
配列 | 文字列: MLLVNQSHQG FNKEHTSKMV SAIVLYVLLA AAAHSAFAVQ LVESGGGLVQ PGGSRKLSCS ASGFAFSSFG MHWVRQAPEK GLEWVAYIS SGSGTIYYAD TVKGRFTISR DDPKNTLFLQ MTSLRSEDTA MYYCVRSIYY YGSSPFDFWG QGTTLTVSAG G GGSGGGGS ...文字列: MLLVNQSHQG FNKEHTSKMV SAIVLYVLLA AAAHSAFAVQ LVESGGGLVQ PGGSRKLSCS ASGFAFSSFG MHWVRQAPEK GLEWVAYIS SGSGTIYYAD TVKGRFTISR DDPKNTLFLQ MTSLRSEDTA MYYCVRSIYY YGSSPFDFWG QGTTLTVSAG G GGSGGGGS GGGGSSDIVM TQATSSVPVT PGESVSISCR SSKSLLHSNG NTYLYWFLQR PGQSPQLLIY RMSNLASGVP DR FSGSGSG TAFTLTISRL EAEDVGVYYC MQHLEYPLTF GAGTKLELVD ENLYFQGASH HHHHHHH |
-分子 #4: 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: 4 / コピー数: 1 / 光学異性体: LEVO |
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由来(天然) | 生物種: Bos taurus (ウシ) |
分子量 | 理論値: 7.861143 KDa |
組換発現 | 生物種: Spodoptera frugiperda (ツマジロクサヨトウ) |
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 #5: Neurokinin-B
分子 | 名称: Neurokinin-B / 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: Homo sapiens (ヒト) |
分子量 | 理論値: 1.212417 KDa |
組換発現 | 生物種: Escherichia coli (大腸菌) |
配列 | 文字列: DMHDFFVGLM UniProtKB: Tachykinin-3 |
-分子 #6: Guanine nucleotide-binding protein Gq (G324)
分子 | 名称: Guanine nucleotide-binding protein Gq (G324) / 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: Homo sapiens (ヒト) |
分子量 | 理論値: 41.694289 KDa |
組換発現 | 生物種: Spodoptera frugiperda (ツマジロクサヨトウ) |
配列 | 文字列: MGCTLSAEDK AAVERSKMIE KQLQKDKQVY RRTLRLLLLG ADNSGKSTIV KQMRIYHVNG YSEEECKQYK AVVYSNTIQS IIAIIRAMG RLKIDFGDSA RADDARQLFV LAGAAEEGFM TAELAGVIKR LWKDSGVQAC FNRSREYQLN DSAAYYLNDL D RIAQPNYI ...文字列: MGCTLSAEDK AAVERSKMIE KQLQKDKQVY RRTLRLLLLG ADNSGKSTIV KQMRIYHVNG YSEEECKQYK AVVYSNTIQS IIAIIRAMG RLKIDFGDSA RADDARQLFV LAGAAEEGFM TAELAGVIKR LWKDSGVQAC FNRSREYQLN DSAAYYLNDL D RIAQPNYI PTQQDVLRTR VKTSGIFETK FQVDKVNFHM FDVGAQRDER RKWIQCFNDV TAIIFVVDSS DYNRLQEALN DF DSIWNNR WLRTISVILF LNKQDLLAEK VLAGKSKIED YFPEFARYTT PEDATPEPGE DPRVTRAKYF IRKEFVDIST ASG DGRHIC YPHFTCAVDT ENARRIFNDC KDIILQMNLR EYNLV |
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
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解析 | 単粒子再構成法 |
試料の集合状態 | particle |
-試料調製
濃度 | 1.0 mg/mL |
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緩衝液 | pH: 7.5 |
凍結 | 凍結剤: ETHANE-PROPANE / チャンバー内湿度: 100 % |
-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 (6k x 4k) / 平均電子線量: 50.0 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: FIELD EMISSION GUN |
電子光学系 | 照射モード: SPOT SCAN / 撮影モード: DIFFRACTION / Cs: 2.7 mm / 最大 デフォーカス(公称値): 2.2 µm / 最小 デフォーカス(公称値): 1.2 µm |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
-画像解析
初期モデル | モデルのタイプ: PDB ENTRY PDBモデル - PDB ID: |
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最終 再構成 | 解像度のタイプ: BY AUTHOR / 解像度: 2.8 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 907878 |
初期 角度割当 | タイプ: ANGULAR RECONSTITUTION |
最終 角度割当 | タイプ: ANGULAR RECONSTITUTION |