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データを開く
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基本情報
| 登録情報 | ![]() | |||||||||
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| タイトル | Cryo-EM structure of Gi coupled Sphingosine 1-phosphate receptor bound with (S)-FTY720-P | |||||||||
マップデータ | ||||||||||
試料 |
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キーワード | GPCR / S1PR1 / SIGNALING PROTEIN | |||||||||
| 機能・相同性 | 機能・相同性情報cardiac muscle tissue growth involved in heart morphogenesis / blood vessel maturation / sphingolipid binding / sphingosine-1-phosphate receptor activity / Lysosphingolipid and LPA receptors / endothelial cell differentiation / heart trabecula morphogenesis / regulation of bone mineralization / negative regulation of stress fiber assembly / sphingosine-1-phosphate receptor signaling pathway ...cardiac muscle tissue growth involved in heart morphogenesis / blood vessel maturation / sphingolipid binding / sphingosine-1-phosphate receptor activity / Lysosphingolipid and LPA receptors / endothelial cell differentiation / heart trabecula morphogenesis / regulation of bone mineralization / negative regulation of stress fiber assembly / sphingosine-1-phosphate receptor signaling pathway / leukocyte chemotaxis / positive regulation of positive chemotaxis / regulation of metabolic process / regulation of bone resorption / lamellipodium assembly / transmission of nerve impulse / regulation of cell adhesion / adenylate cyclase inhibitor activity / positive regulation of protein localization to cell cortex / T cell migration / Adenylate cyclase inhibitory pathway / D2 dopamine receptor binding / response to prostaglandin E / G protein-coupled serotonin receptor binding / adenylate cyclase regulator activity / adenylate cyclase-inhibiting serotonin receptor signaling pathway / positive regulation of smooth muscle cell proliferation / cellular response to forskolin / regulation of mitotic spindle organization / Regulation of insulin secretion / positive regulation of cholesterol biosynthetic process / negative regulation of insulin secretion / G protein-coupled receptor binding / brain development / G protein-coupled receptor activity / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / response to peptide hormone / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / centriolar satellite / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / adenylate cyclase-activating G protein-coupled receptor signaling pathway / chemotaxis / neuron differentiation / 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 / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / G-protein activation / G beta:gamma signalling through CDC42 / Prostacyclin signalling through prostacyclin receptor / 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 / photoreceptor disc membrane / Glucagon-type ligand receptors / Sensory perception of sweet, bitter, and umami (glutamate) taste / GDP binding / Adrenaline,noradrenaline inhibits insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / G alpha (z) signalling events / ADP signalling through P2Y purinoceptor 1 / cellular response to catecholamine stimulus / ADORA2B mediated anti-inflammatory cytokines production / G beta:gamma signalling through PI3Kgamma / cell migration / adenylate cyclase-activating dopamine receptor signaling pathway / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / GPER1 signaling / G-protein beta-subunit binding / cellular response to prostaglandin E stimulus / heterotrimeric G-protein complex / G alpha (12/13) signalling events / Inactivation, recovery and regulation of the phototransduction cascade / extracellular vesicle / sensory perception of taste / presynapse / Thrombin signalling through proteinase activated receptors (PARs) / signaling receptor complex adaptor activity / retina development in camera-type eye / G protein activity / actin cytoskeleton organization / GTPase binding / Ca2+ pathway / fibroblast proliferation / angiogenesis / Interleukin-4 and Interleukin-13 signaling / midbody / cell cortex / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / G alpha (i) signalling events / G alpha (s) signalling events / phospholipase C-activating G protein-coupled receptor signaling pathway / G alpha (q) 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 類似検索 - 分子機能 | |||||||||
| 生物種 | Homo sapiens (ヒト) / ![]() | |||||||||
| 手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 2.83 Å | |||||||||
データ登録者 | Yu LY / Gan B | |||||||||
| 資金援助 | 中国, 1件
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引用 | ジャーナル: Proc Natl Acad Sci U S A / 年: 2022タイトル: Structural insights into sphingosine-1-phosphate receptor activation. 著者: Leiye Yu / Licong He / Bing Gan / Rujuan Ti / Qingjie Xiao / Hongli Hu / Lizhe Zhu / Sheng Wang / Ruobing Ren / ![]() 要旨: As a critical sphingolipid metabolite, sphingosine-1-phosphate (S1P) plays an essential role in immune and vascular systems. There are five S1P receptors, designated as S1PR1 to S1PR5, encoded in the ...As a critical sphingolipid metabolite, sphingosine-1-phosphate (S1P) plays an essential role in immune and vascular systems. There are five S1P receptors, designated as S1PR1 to S1PR5, encoded in the human genome, and their activities are governed by endogenous S1P, lipid-like S1P mimics, or nonlipid-like therapeutic molecules. Among S1PRs, S1PR1 stands out due to its nonredundant functions, such as the egress of T and B cells from the thymus and secondary lymphoid tissues, making it a potential therapeutic target. However, the structural basis of S1PR1 activation and regulation by various agonists remains unclear. Here, we report four atomic resolution cryo-electron microscopy (cryo-EM) structures of Gi-coupled human S1PR1 complexes: bound to endogenous agonist d18:1 S1P, benchmark lipid-like S1P mimic phosphorylated Fingolimod [(S)-FTY720-P], or nonlipid-like therapeutic molecule CBP-307 in two binding modes. Our results revealed the similarities and differences of activation of S1PR1 through distinct ligands binding to the amphiphilic orthosteric pocket. We also proposed a two-step “shallow to deep” transition process of CBP-307 for S1PR1 activation. Both binding modes of CBP-307 could activate S1PR1, but from shallow to deep transition may trigger the rotation of the N-terminal helix of Gαi and further stabilize the complex by increasing the Gαi interaction with the cell membrane. We combine with extensive biochemical analysis and molecular dynamic simulations to suggest key steps of S1P binding and receptor activation. The above results decipher the common feature of the S1PR1 agonist recognition and activation mechanism and will firmly promote the development of therapeutics targeting S1PRs. | |||||||||
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構造の表示
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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_32007.map.gz | 85.8 MB | EMDBマップデータ形式 | |
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| ヘッダ (付随情報) | emd-32007-v30.xml emd-32007.xml | 16.5 KB 16.5 KB | 表示 表示 | EMDBヘッダ |
| 画像 | emd_32007.png | 93.2 KB | ||
| Filedesc metadata | emd-32007.cif.gz | 6.3 KB | ||
| アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-32007 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-32007 | HTTPS FTP |
-関連構造データ
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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 |
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マップ
| ファイル | ダウンロード / ファイル: emd_32007.map.gz / 形式: CCP4 / 大きさ: 91.1 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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| 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: 0.83 Å | ||||||||||||||||||||||||||||||||||||
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| 対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||
| 詳細 | EMDB XML:
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-添付データ
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試料の構成要素
-全体 : S1PR1/Gi complex with FTY720P
| 全体 | 名称: S1PR1/Gi complex with FTY720P |
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| 要素 |
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-超分子 #1: S1PR1/Gi complex with FTY720P
| 超分子 | 名称: S1PR1/Gi complex with FTY720P / タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1-#5 |
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| 由来(天然) | 生物種: Homo sapiens (ヒト) |
-超分子 #2: S1PR1/Gi
| 超分子 | 名称: S1PR1/Gi / タイプ: complex / ID: 2 / 親要素: 1 / 含まれる分子: #1-#2, #4-#5 |
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| 由来(天然) | 生物種: ![]() |
-超分子 #3: scFv16
| 超分子 | 名称: scFv16 / タイプ: complex / ID: 3 / 親要素: 1 / 含まれる分子: #3 |
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-分子 #1: 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: 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: 39.286891 KDa |
| 組換発現 | 生物種: ![]() |
| 配列 | 文字列: HHHHHHLEVL FQGPGSSGSE LDQLRQEAEQ LKNQIRDARK ACADATLSQI TNNIDPVGRI QMRTRRTLRG HLAKIYAMHW GTDSRLLVS ASQDGKLIIW DSYTTNKVHA IPLRSSWVMT CAYAPSGNYV ACGGLDNICS IYNLKTREGN VRVSRELAGH T GYLSCCRF ...文字列: HHHHHHLEVL FQGPGSSGSE LDQLRQEAEQ LKNQIRDARK ACADATLSQI TNNIDPVGRI QMRTRRTLRG HLAKIYAMHW GTDSRLLVS ASQDGKLIIW DSYTTNKVHA IPLRSSWVMT CAYAPSGNYV ACGGLDNICS IYNLKTREGN VRVSRELAGH T GYLSCCRF LDDNQIVTSS GDTTCALWDI ETGQQTTTFT GHTGDVMSLS LAPDTRLFVS GACDASAKLW DVREGMCRQT FT GHESDIN AICFFPNGNA FATGSDDATC RLFDLRADQE LMTYSHDNII CGITSVSFSK SGRLLLAGYD DFNCNVWDAL KAD RAGVLA GHDNRVSCLG VTDDGMAVAT GSWDSFLKIW N UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 |
-分子 #2: 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: 2 / 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: 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 #3: scFv16
| 分子 | 名称: scFv16 / 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: 26.679721 KDa |
| 組換発現 | 生物種: Trichoplusia ni (イラクサキンウワバ) |
| 配列 | 文字列: DVQLVESGGG LVQPGGSRKL SCSASGFAFS SFGMHWVRQA PEKGLEWVAY ISSGSGTIYY ADTVKGRFTI SRDDPKNTLF LQMTSLRSE DTAMYYCVRS IYYYGSSPFD FWGQGTTLTV SSGGGGSGGG GSGGGGSDIV MTQATSSVPV TPGESVSISC R SSKSLLHS ...文字列: DVQLVESGGG LVQPGGSRKL SCSASGFAFS SFGMHWVRQA PEKGLEWVAY ISSGSGTIYY ADTVKGRFTI SRDDPKNTLF LQMTSLRSE DTAMYYCVRS IYYYGSSPFD FWGQGTTLTV SSGGGGSGGG GSGGGGSDIV MTQATSSVPV TPGESVSISC R SSKSLLHS NGNTYLYWFL QRPGQSPQLL IYRMSNLASG VPDRFSGSGS GTAFTLTISR LEAEDVGVYY CMQHLEYPLT FG AGTKLEL KAAA |
-分子 #4: Sphingosine 1-phosphate receptor 1
| 分子 | 名称: Sphingosine 1-phosphate receptor 1 / 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: Homo sapiens (ヒト) |
| 分子量 | 理論値: 44.483441 KDa |
| 組換発現 | 生物種: ![]() |
| 配列 | 文字列: MGPTSVPLVK AHRSSVSDYV NYDIIVRHYN YTGKLNISAD KENSIKLTSV VFILICCFII LENIFVLLTI WKTKKFHRPM YYFIGNLAL SDLLAGVAYT ANLLLSGATT YKLTPAQWFL REGSMFVALS ASVFSLLAIA IERYITMLKM KLHNGSNNFR L FLLISACW ...文字列: MGPTSVPLVK AHRSSVSDYV NYDIIVRHYN YTGKLNISAD KENSIKLTSV VFILICCFII LENIFVLLTI WKTKKFHRPM YYFIGNLAL SDLLAGVAYT ANLLLSGATT YKLTPAQWFL REGSMFVALS ASVFSLLAIA IERYITMLKM KLHNGSNNFR L FLLISACW VISLILGGLP IMGWNCISAL SSCSTVLPLY HKHYILFCTT VFTLLLLSIV ILYCRIYSLV RTRSRRLTFR KN ISKASRS SEKSLALLKT VIIVLSVFIA CWAPLFILLL LDVGCKVKTC DILFRAEYFL VLAVLNSGTN PIIYTLTNKE MRR AFIRIM SCCKCPSGDS AGKFKRPIIA GMEFSRSKSD NSSHPQKDEG DNPETIMSSG NVNSSSLEHH HHHHHHHH UniProtKB: Sphingosine 1-phosphate receptor 1 |
-分子 #5: Guanine nucleotide-binding protein G(i) subunit alpha-1
| 分子 | 名称: Guanine nucleotide-binding protein G(i) subunit alpha-1 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: 40.415031 KDa |
| 組換発現 | 生物種: ![]() |
| 配列 | 文字列: MGCTLSAEDK AAVERSKMID RNLREDGEKA AREVKLLLLG AGESGKSTIV KQMKIIHEAG YSEEECKQYK AVVYSNTIQS IIAIIRAMG RLKIDFGDSA RADDARQLFV LAGAAEEGFM TAELAGVIKR LWKDSGVQAC FNRSREYQLN DSAAYYLNDL D RIAQPNYI ...文字列: MGCTLSAEDK AAVERSKMID RNLREDGEKA AREVKLLLLG AGESGKSTIV KQMKIIHEAG YSEEECKQYK AVVYSNTIQS IIAIIRAMG RLKIDFGDSA RADDARQLFV LAGAAEEGFM TAELAGVIKR LWKDSGVQAC FNRSREYQLN DSAAYYLNDL D RIAQPNYI PTQQDVLRTR VKTTGIVETH FTFKDLHFKM FDVGGQRSER KKWIHCFEGV TAIIFCVALS DYDLVLAEDE EM NRMHESM KLFDSICNNK WFTDTSIILF LNKKDLFEEK IKKSPLTICY PEYAGSNTYE EAAAYIQCQF EDLNKRKDTK EIY THFTCA TDTKNVQFVF DAVTDVIIKN NLKDCGLF UniProtKB: Guanine nucleotide-binding protein G(i) subunit alpha-1 |
-分子 #6: (2~{S})-2-azanyl-4-(4-octylphenyl)-2-[[oxidanyl-bis(oxidanylidene...
| 分子 | 名称: (2~{S})-2-azanyl-4-(4-octylphenyl)-2-[[oxidanyl-bis(oxidanylidene)-$l^{6}-phosphanyl]oxymethyl]butan-1-ol タイプ: ligand / ID: 6 / コピー数: 1 / 式: J89 |
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| 分子量 | 理論値: 387.451 Da |
| Chemical component information | ![]() ChemComp-J89: |
-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 |
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試料調製
| 緩衝液 | pH: 7.5 |
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| 凍結 | 凍結剤: ETHANE |
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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 (6k x 4k) / 平均電子線量: 56.2 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: FLOOD BEAM / 撮影モード: BRIGHT FIELD 最大 デフォーカス(公称値): 1.9000000000000001 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 |
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画像解析
| 初期モデル | モデルのタイプ: OTHER 詳細: initial model was obtained from ab initio reconstruction using cryoSPARC |
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| 最終 再構成 | 解像度のタイプ: BY AUTHOR / 解像度: 2.83 Å / 解像度の算出法: FSC 0.143 CUT-OFF 詳細: EVEN/ODD MAPS REFINED TOTALLY INDIPENDENT (gold standard) for half map 使用した粒子像数: 788201 |
| 初期 角度割当 | タイプ: MAXIMUM LIKELIHOOD |
| 最終 角度割当 | タイプ: MAXIMUM LIKELIHOOD |
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万見について




キーワード
Homo sapiens (ヒト)
データ登録者
中国, 1件
引用


































Z (Sec.)
Y (Row.)
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FIELD EMISSION GUN
