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基本情報
登録情報 | ![]() | |||||||||
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タイトル | Lysophosphatidylserine receptor GPR174-Gs complex | |||||||||
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![]() | Complex / SIGNALING PROTEIN | |||||||||
機能・相同性 | ![]() bioactive lipid receptor activity / negative regulation of interleukin-2 production / T cell homeostasis / PKA activation in glucagon signalling / developmental growth / hair follicle placode formation / D1 dopamine receptor binding / intracellular transport / vascular endothelial cell response to laminar fluid shear stress / renal water homeostasis ...bioactive lipid receptor activity / negative regulation of interleukin-2 production / T cell homeostasis / PKA activation in glucagon signalling / developmental growth / hair follicle placode formation / D1 dopamine receptor binding / intracellular transport / vascular endothelial cell response to laminar fluid shear stress / renal water homeostasis / activation of adenylate cyclase activity / Hedgehog 'off' state / adenylate cyclase-activating adrenergic receptor signaling pathway / cellular response to glucagon stimulus / regulation of insulin secretion / adenylate cyclase activator activity / trans-Golgi network membrane / negative regulation of inflammatory response to antigenic stimulus / G protein-coupled receptor activity / bone development / centriolar satellite / platelet aggregation / G-protein beta/gamma-subunit complex binding / cognition / 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 / adenylate cyclase-activating G protein-coupled receptor signaling pathway / 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 / 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 / sensory perception of smell / 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 / sensory perception of taste / extracellular vesicle / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / positive regulation of cold-induced thermogenesis / retina development in camera-type eye / G protein activity / GTPase binding / Ca2+ pathway / fibroblast proliferation / 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 / 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 / G alpha (q) signalling events / Ras protein signal transduction / Extra-nuclear estrogen signaling / cell population proliferation / G protein-coupled receptor signaling pathway / lysosomal membrane / intracellular membrane-bounded organelle / GTPase activity / synapse / GTP binding / protein-containing complex binding / signal transduction / extracellular exosome / metal ion binding / membrane / plasma membrane / cytosol / cytoplasm 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: 3.06 Å | |||||||||
![]() | Gong W / Liu G / Li X / Zhang X | |||||||||
資金援助 | 1件
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![]() | ![]() タイトル: Structural basis for ligand recognition and signaling of the lysophosphatidylserine receptors GPR34 and GPR174. 著者: Guibing Liu / Xiu Li / Yujing Wang / Xuan Zhang / Weimin Gong / ![]() ![]() 要旨: Lysophosphatidylserine (LysoPS) is a naturally occurring lipid mediator involved in various physiological and pathological processes especially those related to the immune system. GPR34, GPR174, and ...Lysophosphatidylserine (LysoPS) is a naturally occurring lipid mediator involved in various physiological and pathological processes especially those related to the immune system. GPR34, GPR174, and P2Y10 have been identified as the receptors for LysoPS, and its analogues have been developed as agonists or antagonists for these receptors. However, the lack of structural information hinders the drug development with novel characteristics, such as nonlipid ligands and allosteric modulators. Here, we determined the structures of human GPR34 and GPR174 in complex with LysoPS and G protein by cryo-EM. Combined with structural analysis and functional studies, we elucidated the lipid-binding modes of these receptors. By structural comparison, we identified the structural features of GPR34 and GPR174 in active state. Taken together, our findings provide insights into ligand recognition and signaling of LysoPS receptors and will facilitate the development of novel therapeutics for related inflammatory diseases and autoimmune diseases. | |||||||||
履歴 |
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構造の表示
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-EMDBアーカイブ
マップデータ | ![]() | 1.4 MB | ![]() | |
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ヘッダ (付随情報) | ![]() ![]() | 19.3 KB 19.3 KB | 表示 表示 | ![]() |
画像 | ![]() | 126.7 KB | ||
Filedesc metadata | ![]() | 6.5 KB | ||
その他 | ![]() ![]() | 25 MB 25 MB | ||
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-検証レポート
文書・要旨 | ![]() | 816.1 KB | 表示 | ![]() |
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文書・詳細版 | ![]() | 815.8 KB | 表示 | |
XML形式データ | ![]() | 10.5 KB | 表示 | |
CIF形式データ | ![]() | 12.3 KB | 表示 | |
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 | ![]() 8izbMC ![]() 8wrbC 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 ( |
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類似構造データ | 類似検索 - 機能・相同性 ![]() |
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リンク
EMDBのページ | ![]() ![]() |
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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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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: #2
ファイル | emd_35838_half_map_1.map | ||||||||||||
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投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: #1
ファイル | emd_35838_half_map_2.map | ||||||||||||
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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 : LysoPS-bound GPR174 in complex with Gs and Nb35.
全体 | 名称: LysoPS-bound GPR174 in complex with Gs and Nb35. |
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要素 |
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-超分子 #1: LysoPS-bound GPR174 in complex with Gs and Nb35.
超分子 | 名称: LysoPS-bound GPR174 in complex with Gs and Nb35. / 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: ![]() |
-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 |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 29.048932 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: MGCLGNSKTE DQRNEEKAQR EANKMIEKQL QKDKQVYRAT HRLLLLGADN SGKSTIVKQM RIYHVNSGIF ETKFQVDKVN FHMFDVGAQ RDERRKWIQC FNDVTAIIFV VDSSDYNRLQ EALNDFKSIW NNRWLRTISV ILFLNKQDLL AEKVLAGKSK I EDYFPEFA ...文字列: MGCLGNSKTE DQRNEEKAQR EANKMIEKQL QKDKQVYRAT HRLLLLGADN SGKSTIVKQM RIYHVNSGIF ETKFQVDKVN FHMFDVGAQ RDERRKWIQC FNDVTAIIFV VDSSDYNRLQ EALNDFKSIW NNRWLRTISV ILFLNKQDLL AEKVLAGKSK I EDYFPEFA RYTTPEDATP EPGEDPRVTR AKYFIRDEFL RISTASGDGR HYCYPHFTCS VDTENARRIF NDCRDIIQRM HL RQYELL 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 |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 40.845559 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: MHHHHHHGSS GSELDQLRQE AEQLKNQIRD ARKACADATL SQITNNIDPV GRIQMRTRRT LRGHLAKIYA MHWGTDSRLL VSASQDGKL IIWDSYTTNK VHAIPLRSSW VMTCAYAPSG NYVACGGLDN ICSIYNLKTR EGNVRVSREL AGHTGYLSCC R FLDDNQIV ...文字列: MHHHHHHGSS GSELDQLRQE AEQLKNQIRD ARKACADATL SQITNNIDPV GRIQMRTRRT LRGHLAKIYA MHWGTDSRLL VSASQDGKL IIWDSYTTNK VHAIPLRSSW VMTCAYAPSG NYVACGGLDN ICSIYNLKTR EGNVRVSREL AGHTGYLSCC R FLDDNQIV TSSGDTTCAL WDIETGQQTT TFTGHTGDVM SLSLAPDTRL FVSGACDASA KLWDVREGMC RQTFTGHESD IN AICFFPN GNAFATGSDD ATCRLFDLRA DQELMTYSHD NIICGITSVS FSKSGRLLLA GYDDFNCNVW DALKADRAGV LAG HDNRVS CLGVTDDGMA VATGSWDSFL KIWNGSSGGG GSGGGGSSGV SGWRLFKKIS 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: Nanobody35
分子 | 名称: Nanobody35 / 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: synthetic construct (人工物) |
分子量 | 理論値: 15.140742 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: QVQLQESGGG LVQPGGSLRL SCAASGFTFS NYKMNWVRQA PGKGLEWVSD ISQSGASISY TGSVKGRFTI SRDNAKNTLY LQMNSLKPE DTAVYYCARC PAPFTRDCFD VTSTTYAYRG QGTQVTVSSH HHHHHEPEA |
-分子 #5: Probable G-protein coupled receptor 174
分子 | 名称: Probable G-protein coupled receptor 174 / 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: 63.90818 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: DYKDDDDHHH HHHHHGQPGN GSAFLLAPNG SHAPDHNVTQ QRDEGGSGQP GNGSAFLLAP NGSHAPDHNV TQQRDEENLY FQGVDMPAN YTCTRPDGDN TDFRYFIYAV TYTVILVPGL IGNILALWVF YGYMKETKRA VIFMINLAIA DLLQVLSLPL R IFYYLNHD ...文字列: DYKDDDDHHH HHHHHGQPGN GSAFLLAPNG SHAPDHNVTQ QRDEGGSGQP GNGSAFLLAP NGSHAPDHNV TQQRDEENLY FQGVDMPAN YTCTRPDGDN TDFRYFIYAV TYTVILVPGL IGNILALWVF YGYMKETKRA VIFMINLAIA DLLQVLSLPL R IFYYLNHD WPFGPGLCMF CFYLKYVNMY ASIYFLVCIS VRRFWFLMYP FRFHDCKQKY DLYISIAGWL IICLACVLFP LL RTSDDTS GNRTKCFVDL PTRNVNLAQS VVMMTIGELI GFVTPLLIVL YCTWKTVLSL QDKYPMAQDL GEKQKALKMI LTC AGVFLI CFAPYHFSFP LDFLVKSNEI KSCLARRVIL IFHSVALCLA SLNSCLDPVI YYFSTNEFRR RLSRQDLHMG SSGG GGSGG GGSSGVFTLE DFVGDWEQTA AYNLDQVLEQ GGVSSLLQNL AVSVTPIQRI VRSGENALKI DIHVIIPYEG LSADQ MAQI EEVFKVVYPV DDHHFKVILP YGTLVIDGVT PNMLNYFGRP YEGIAVFDGK KITVTGTLWN GNKIIDERLI TPDGSM LFR VTINS UniProtKB: Probable G-protein coupled receptor 174 |
-分子 #6: [(2R)-2-oxidanyl-3-phosphonooxy-propyl] (Z)-octadec-9-enoate
分子 | 名称: [(2R)-2-oxidanyl-3-phosphonooxy-propyl] (Z)-octadec-9-enoate タイプ: ligand / ID: 6 / コピー数: 1 / 式: UBL |
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分子量 | 理論値: 436.52 Da |
Chemical component information | ![]() ChemComp-UBL: |
-分子 #7: SERINE
分子 | 名称: SERINE / タイプ: ligand / ID: 7 / コピー数: 1 / 式: SER |
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分子量 | 理論値: 105.093 Da |
Chemical component information | ![]() ChemComp-SER: |
-分子 #8: CHOLESTEROL
分子 | 名称: CHOLESTEROL / タイプ: ligand / ID: 8 / コピー数: 2 / 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
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 BIOQUANTUM (6k x 4k) 平均電子線量: 55.0 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): 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 |
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画像解析
初期モデル | モデルのタイプ: INSILICO MODEL |
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最終 再構成 | 解像度のタイプ: BY AUTHOR / 解像度: 3.06 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 132808 |
初期 角度割当 | タイプ: PROJECTION MATCHING |
最終 角度割当 | タイプ: PROJECTION MATCHING |