+
データを開く
-
基本情報
登録情報 | ![]() | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
タイトル | Cryo-EM structure of Latanoprost-bound prostaglandin-F2-alpha receptor-miniGq-Nb35 complex | |||||||||
![]() | ||||||||||
![]() |
| |||||||||
![]() | GPCR / Complex / Prostaglandin receptor / Agonist / MEMBRANE PROTEIN | |||||||||
機能・相同性 | ![]() prostaglandin F receptor activity / parturition / Prostanoid ligand receptors / cellular response to prostaglandin D stimulus / PKA activation in glucagon signalling / hair follicle placode formation / developmental growth / D1 dopamine receptor binding / intracellular transport / Hedgehog 'off' state ...prostaglandin F receptor activity / parturition / Prostanoid ligand receptors / cellular response to prostaglandin D stimulus / PKA activation in glucagon signalling / hair follicle placode formation / developmental growth / D1 dopamine receptor binding / intracellular transport / Hedgehog 'off' state / adenylate cyclase-activating adrenergic receptor signaling pathway / activation of adenylate cyclase activity / adenylate cyclase activator activity / trans-Golgi network membrane / G-protein beta/gamma-subunit complex binding / bone development / 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 / adenylate cyclase-activating G protein-coupled receptor signaling pathway / 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 / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / cognition / platelet aggregation / ADP signalling through P2Y purinoceptor 12 / G beta:gamma signalling through BTK / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / Sensory perception of sweet, bitter, and umami (glutamate) taste / photoreceptor disc membrane / Adrenaline,noradrenaline inhibits insulin secretion / Glucagon-type ligand receptors / Vasopressin regulates renal water homeostasis via Aquaporins / G alpha (z) signalling events / cellular response to catecholamine stimulus / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / ADORA2B mediated anti-inflammatory cytokines production / sensory perception of taste / ADP signalling through P2Y purinoceptor 1 / adenylate cyclase-activating dopamine receptor signaling pathway / G beta:gamma signalling through PI3Kgamma / cellular response to prostaglandin E stimulus / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / GPER1 signaling / G-protein beta-subunit binding / Inactivation, recovery and regulation of the phototransduction cascade / heterotrimeric G-protein complex / G alpha (12/13) signalling events / extracellular vesicle / sensory perception of smell / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / response to estradiol / GTPase binding / retina development in camera-type eye / Ca2+ pathway / positive regulation of cold-induced thermogenesis / phospholipase C-activating G protein-coupled receptor signaling pathway / positive regulation of cytosolic calcium ion concentration / G alpha (i) signalling events / fibroblast proliferation / G alpha (s) signalling events / Ras protein signal transduction / G alpha (q) signalling events / Extra-nuclear estrogen signaling / cell population proliferation / response to lipopolysaccharide / inflammatory response / G protein-coupled receptor signaling pathway / lysosomal membrane / GTPase activity / positive regulation of cell population proliferation / synapse / positive regulation of gene expression / negative regulation of apoptotic process / protein-containing complex binding / GTP binding / signal transduction / extracellular exosome / extracellular region / membrane / metal ion binding / plasma membrane / cytoplasm / cytosol 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: 3.4 Å | |||||||||
![]() | Lv X / Gao K / Nie J / Zhang X / Zhang S / Ren Y / Li Q / Huang J / Liu L / Sun X ...Lv X / Gao K / Nie J / Zhang X / Zhang S / Ren Y / Li Q / Huang J / Liu L / Sun X / Zhang W / Liu X | |||||||||
資金援助 | ![]()
| |||||||||
![]() | ![]() タイトル: Structures of human prostaglandin F receptor reveal the mechanism of ligand and G protein selectivity. 著者: Xiuqing Lv / Kaixuan Gao / Jia Nie / Xin Zhang / Shuhao Zhang / Yinhang Ren / Xiaoou Sun / Qi Li / Jingrui Huang / Lijuan Liu / Xiaowen Zhang / Weishe Zhang / Xiangyu Liu / ![]() 要旨: Prostaglandins and their receptors regulate various physiological processes. Carboprost, an analog of prostaglandin F and an agonist for the prostaglandin F2-alpha receptor (FP receptor), is ...Prostaglandins and their receptors regulate various physiological processes. Carboprost, an analog of prostaglandin F and an agonist for the prostaglandin F2-alpha receptor (FP receptor), is clinically used to treat postpartum hemorrhage (PPH). However, off-target activation of closely related receptors such as the prostaglandin E receptor subtype EP3 (EP3 receptor) by carboprost results in side effects and limits the clinical application. Meanwhile, the FP receptor selective agonist latanoprost is not suitable to treat PPH due to its poor solubility and fast clearance. Here, we present two cryo-EM structures of the FP receptor bound to carboprost and latanoprost-FA (the free acid form of latanoprost) at 2.7 Å and 3.2 Å resolution, respectively. The structures reveal the molecular mechanism of FP receptor selectivity for both endogenous prostaglandins and clinical drugs, as well as the molecular mechanism of G protein coupling preference by the prostaglandin receptors. The structural information may guide the development of better prostaglandin drugs. | |||||||||
履歴 |
|
-
構造の表示
添付画像 |
---|
-
ダウンロードとリンク
-EMDBアーカイブ
マップデータ | ![]() | 59.6 MB | ![]() | |
---|---|---|---|---|
ヘッダ (付随情報) | ![]() ![]() | 19.6 KB 19.6 KB | 表示 表示 | ![]() |
画像 | ![]() | 67.3 KB | ||
マスクデータ | ![]() | 64 MB | ![]() | |
Filedesc metadata | ![]() | 6.6 KB | ||
その他 | ![]() ![]() | 59.4 MB 59.4 MB | ||
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-関連構造データ
関連構造データ | ![]() 8iq6MC ![]() 8iq4C M: このマップから作成された原子モデル C: 同じ文献を引用 ( |
---|---|
類似構造データ | 類似検索 - 機能・相同性 ![]() |
-
リンク
EMDBのページ | ![]() ![]() |
---|---|
「今月の分子」の関連する項目 |
-
マップ
ファイル | ![]() | ||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
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: 1.0979 Å | ||||||||||||||||||||||||||||||||||||
密度 |
| ||||||||||||||||||||||||||||||||||||
対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
|
-添付データ
-マスク #1
ファイル | ![]() | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
投影像・断面図 |
| ||||||||||||
密度ヒストグラム |
-ハーフマップ: #2
ファイル | emd_35658_half_map_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
投影像・断面図 |
| ||||||||||||
密度ヒストグラム |
-ハーフマップ: #1
ファイル | emd_35658_half_map_2.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
投影像・断面図 |
| ||||||||||||
密度ヒストグラム |
-
試料の構成要素
-全体 : Cryo-EM structure of Latanoprost-bound prostaglandin-F2-alpha rec...
全体 | 名称: Cryo-EM structure of Latanoprost-bound prostaglandin-F2-alpha receptor-miniGq-Nb35 complex |
---|---|
要素 |
|
-超分子 #1: Cryo-EM structure of Latanoprost-bound prostaglandin-F2-alpha rec...
超分子 | 名称: Cryo-EM structure of Latanoprost-bound prostaglandin-F2-alpha receptor-miniGq-Nb35 complex タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1-#5 |
---|---|
由来(天然) | 生物種: ![]() |
-分子 #1: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short
分子 | 名称: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short タイプ: protein_or_peptide / ID: 1 / コピー数: 1 / 光学異性体: LEVO |
---|---|
由来(天然) | 生物種: ![]() |
分子量 | 理論値: 28.168926 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: GPTLSAEDKA AVERSKMIEK QLQKDKQVYR ATHRLLLLGA DNSGKSTIVK QMRILHGGSG GSGGTSGIFE TKFQVDKVNF HMFDVGGQR DERRKWIQCF NDVTAIIFVV DSSDYNRLQE ALNDFKSIWN NRWLRTISVI LFLNKQDLLA EKVLAGKSKI E DYFPEFAR ...文字列: GPTLSAEDKA AVERSKMIEK QLQKDKQVYR ATHRLLLLGA DNSGKSTIVK QMRILHGGSG GSGGTSGIFE TKFQVDKVNF HMFDVGGQR DERRKWIQCF NDVTAIIFVV DSSDYNRLQE ALNDFKSIWN NRWLRTISVI LFLNKQDLLA EKVLAGKSKI E DYFPEFAR YTTPEDATPE PGEDPRVTRA KYFIRDEFLR ISTASGDGRH YCYPHFTCAV DTENARRIFN DCKDIILQMN LR EYNLV UniProtKB: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short, Guanine nucleotide-binding protein G(s) subunit alpha isoforms short |
-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 |
---|---|
由来(天然) | 生物種: ![]() |
分子量 | 理論値: 39.418086 KDa |
組換発現 | 生物種: ![]() |
配列 | 文字列: MHHHHHHLEV LFQGPGSSGS ELDQLRQEAE QLKNQIRDAR KACADATLSQ ITNNIDPVGR IQMRTRRTLR GHLAKIYAMH WGTDSRLLV SASQDGKLII WDSYTTNKVH AIPLRSSWVM TCAYAPSGNY VACGGLDNIC SIYNLKTREG NVRVSRELAG H TGYLSCCR ...文字列: MHHHHHHLEV LFQGPGSSGS ELDQLRQEAE QLKNQIRDAR KACADATLSQ ITNNIDPVGR IQMRTRRTLR GHLAKIYAMH WGTDSRLLV SASQDGKLII WDSYTTNKVH AIPLRSSWVM TCAYAPSGNY VACGGLDNIC SIYNLKTREG NVRVSRELAG H TGYLSCCR FLDDNQIVTS SGDTTCALWD IETGQQTTTF TGHTGDVMSL SLAPDTRLFV SGACDASAKL WDVREGMCRQ TF TGHESDI NAICFFPNGN AFATGSDDAT CRLFDLRADQ ELMTYSHDNI ICGITSVSFS KSGRLLLAGY DDFNCNVWDA LKA DRAGVL AGHDNRVSCL GVTDDGMAVA TGSWDSFLKI WN 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 |
---|---|
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: Nanobody 35
分子 | 名称: Nanobody 35 / タイプ: protein_or_peptide / ID: 4 / コピー数: 1 / 光学異性体: LEVO |
---|---|
由来(天然) | 生物種: ![]() ![]() |
分子量 | 理論値: 14.686328 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: QVQLQESGGG LVQPGGSLRL SCAASGFTFS NYKMNWVRQA PGKGLEWVSD ISQSGASISY TGSVKGRFTI SRDNAKNTLY LQMNSLKPE DTAVYYCARC PAPFTPFCFD VTSTTYAYRG QGTQVTVSSH HHHHH |
-分子 #5: Prostaglandin F2-alpha receptor
分子 | 名称: Prostaglandin F2-alpha receptor / タイプ: protein_or_peptide / ID: 5 / コピー数: 1 / 光学異性体: LEVO |
---|---|
由来(天然) | 生物種: ![]() |
分子量 | 理論値: 42.909363 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: DYKDDDDAMS MNNSKQLVSP AAALLSNTTC QTENRLSVFF SVIFMTVGIL SNSLAIAILM KAYQRFRQKS KASFLLLASG LVITDFFGH LINGAIAVFV YASDKEWIRF DQSNVLCSIF GICMVFSGLC PLLLGSVMAI ERCIGVTKPI FHSTKITSKH V KMMLSGVC ...文字列: DYKDDDDAMS MNNSKQLVSP AAALLSNTTC QTENRLSVFF SVIFMTVGIL SNSLAIAILM KAYQRFRQKS KASFLLLASG LVITDFFGH LINGAIAVFV YASDKEWIRF DQSNVLCSIF GICMVFSGLC PLLLGSVMAI ERCIGVTKPI FHSTKITSKH V KMMLSGVC LFAVFIALLP ILGHRDYKIQ ASRTWCFYNT EDIKDWEDRF YLLLFSFLGL LALGVSLLCN AITGITLLRV KF KSQQHRQ GRSHHLEMVI QLLAIMCVSC ICWSPFLVTM ANIGINGNHS LETCETTLFA LRMATWNQIL DPWVYILLRK AVL KNLYKL ASQCCGVHVI SLHIWELSSI KNSLKVAAIS ESPVAEKSAS THHHHHHGGS GGLEVLFQ UniProtKB: Prostaglandin F2-alpha receptor |
-分子 #6: Z-7-[(1R,2R,3R,5S)-3,5-bis(oxidanyl)-2-[(3R)-3-oxidanyl-5-phenyl-...
分子 | 名称: Z-7-[(1R,2R,3R,5S)-3,5-bis(oxidanyl)-2-[(3R)-3-oxidanyl-5-phenyl-pentyl]cyclopentyl]hept-5-enoic acid タイプ: ligand / ID: 6 / コピー数: 1 / 式: 7WT |
---|---|
分子量 | 理論値: 390.513 Da |
Chemical component information | ![]() ChemComp-7WT: |
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
---|---|
![]() | 単粒子再構成法 |
試料の集合状態 | particle |
-
試料調製
緩衝液 | pH: 7.45 |
---|---|
凍結 | 凍結剤: ETHANE |
-
電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
---|---|
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: ![]() |
電子光学系 | 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELD / 最大 デフォーカス(公称値): 1.8 µm / 最小 デフォーカス(公称値): 1.1 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: NONE |
---|---|
最終 再構成 | 解像度のタイプ: BY AUTHOR / 解像度: 3.4 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 132183 |
初期 角度割当 | タイプ: MAXIMUM LIKELIHOOD |
最終 角度割当 | タイプ: MAXIMUM LIKELIHOOD |