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基本情報
登録情報 | ![]() | |||||||||
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タイトル | Cryo-EM structure of the TUG891 bound GPR120-Giq complex | |||||||||
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機能・相同性 | ![]() negative regulation of somatostatin secretion / ghrelin secretion / positive regulation of glucagon secretion / Free fatty acid receptors / regulation of glucose transmembrane transport / taste receptor activity / Fatty Acids bound to GPR40 (FFAR1) regulate insulin secretion / Acetylcholine regulates insulin secretion / PLC beta mediated events / phospholipase C-activating dopamine receptor signaling pathway ...negative regulation of somatostatin secretion / ghrelin secretion / positive regulation of glucagon secretion / Free fatty acid receptors / regulation of glucose transmembrane transport / taste receptor activity / Fatty Acids bound to GPR40 (FFAR1) regulate insulin secretion / Acetylcholine regulates insulin secretion / PLC beta mediated events / phospholipase C-activating dopamine receptor signaling pathway / entrainment of circadian clock / regulation of platelet activation / hormone secretion / phototransduction, visible light / arrestin family protein binding / glutamate receptor signaling pathway / : / regulation of canonical Wnt signaling pathway / white fat cell differentiation / negative regulation of cytokine production / ciliary membrane / negative regulation of interleukin-1 beta production / action potential / endocytic vesicle / photoreceptor outer segment / Adenylate cyclase inhibitory pathway / positive regulation of protein localization to cell cortex / regulation of cAMP-mediated signaling / positive regulation of osteoblast differentiation / D2 dopamine receptor binding / G protein-coupled serotonin receptor binding / brown fat cell differentiation / regulation of mitotic spindle organization / cellular response to hormone stimulus / cellular response to forskolin / positive regulation of brown fat cell differentiation / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / GTPase activator activity / peptide binding / Regulation of insulin secretion / fatty acid binding / G protein-coupled receptor binding / G protein-coupled receptor activity / negative regulation of protein kinase activity / negative regulation of inflammatory response / G-protein beta/gamma-subunit complex binding / Olfactory Signaling Pathway / Activation of the phototransduction cascade / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / 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 / cilium / Prostacyclin signalling through prostacyclin receptor / Glucagon signaling in metabolic regulation / G beta:gamma signalling through CDC42 / response to peptide hormone / 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 / GDP binding / G-protein beta-subunit binding / Inactivation, recovery and regulation of the phototransduction cascade / heterotrimeric G-protein complex / G alpha (12/13) signalling events / blood coagulation / extracellular vesicle / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / 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 / cell cortex / positive regulation of cytosolic calcium ion concentration / midbody / G alpha (i) signalling events / nuclear membrane 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: 2.64 Å | |||||||||
![]() | Mao C / Xiao P / Tao X / Qin J / He Q / Zhang C / Yu X / Zhang Y / Sun J | |||||||||
資金援助 | 1件
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![]() | ![]() タイトル: Unsaturated bond recognition leads to biased signal in a fatty acid receptor. 著者: Chunyou Mao / Peng Xiao / Xiao-Na Tao / Jiao Qin / Qing-Tao He / Chao Zhang / Sheng-Chao Guo / Ya-Qin Du / Li-Nan Chen / Dan-Dan Shen / Zhi-Shuai Yang / Han-Qiong Zhang / Shen-Ming Huang / ...著者: Chunyou Mao / Peng Xiao / Xiao-Na Tao / Jiao Qin / Qing-Tao He / Chao Zhang / Sheng-Chao Guo / Ya-Qin Du / Li-Nan Chen / Dan-Dan Shen / Zhi-Shuai Yang / Han-Qiong Zhang / Shen-Ming Huang / Yong-Hao He / Jie Cheng / Ya-Ni Zhong / Pan Shang / Jun Chen / Dao-Lai Zhang / Qian-Lang Wang / Mei-Xia Liu / Guo-Yu Li / Yongyuan Guo / H Eric Xu / Chuanxin Wang / Cheng Zhang / Shiqing Feng / Xiao Yu / Yan Zhang / Jin-Peng Sun / ![]() 要旨: Individual free fatty acids (FAs) play important roles in metabolic homeostasis, many through engagement with more than 40G protein-coupled receptors. Searching for receptors to sense beneficial ...Individual free fatty acids (FAs) play important roles in metabolic homeostasis, many through engagement with more than 40G protein-coupled receptors. Searching for receptors to sense beneficial omega-3 FAs of fish oil enabled the identification of GPR120, which is involved in a spectrum of metabolic diseases. Here, we report six cryo-electron microscopy structures of GPR120 in complex with FA hormones or TUG891 and G or G trimers. Aromatic residues inside the GPR120 ligand pocket were responsible for recognizing different double-bond positions of these FAs and connect ligand recognition to distinct effector coupling. We also investigated synthetic ligand selectivity and the structural basis of missense single-nucleotide polymorphisms. We reveal how GPR120 differentiates rigid double bonds and flexible single bonds. The knowledge gleaned here may facilitate rational drug design targeting to GPR120. | |||||||||
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マップデータ | ![]() | 882.7 KB | ![]() | |
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画像 | ![]() | 81.7 KB | ||
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「今月の分子」の関連する項目 |
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ファイル | ![]() | ||||||||||||||||||||
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ボクセルのサイズ | X=Y=Z: 1.014 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 : Cryo-EM structure of the TUG891 bound GPR120-Giq complex
全体 | 名称: Cryo-EM structure of the TUG891 bound GPR120-Giq complex |
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要素 |
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-超分子 #1: Cryo-EM structure of the TUG891 bound GPR120-Giq complex
超分子 | 名称: Cryo-EM structure of the TUG891 bound GPR120-Giq complex タイプ: complex / ID: 1 / キメラ: Yes / 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(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: ![]() |
分子量 | 理論値: 37.285734 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: SELDQLRQEA EQLKNQIRDA RKACADATLS QITNNIDPVG RIQMRTRRTL RGHLAKIYAM HWGTDSRLLV SASQDGKLII WDSYTTNKV HAIPLRSSWV MTCAYAPSGN YVACGGLDNI CSIYNLKTRE GNVRVSRELA GHTGYLSCCR FLDDNQIVTS S GDTTCALW ...文字列: SELDQLRQEA EQLKNQIRDA RKACADATLS QITNNIDPVG RIQMRTRRTL RGHLAKIYAM HWGTDSRLLV SASQDGKLII WDSYTTNKV HAIPLRSSWV MTCAYAPSGN YVACGGLDNI CSIYNLKTRE GNVRVSRELA GHTGYLSCCR FLDDNQIVTS S GDTTCALW DIETGQQTTT FTGHTGDVMS LSLAPDTRLF VSGACDASAK LWDVREGMCR QTFTGHESDI NAICFFPNGN AF ATGSDDA TCRLFDLRAD QELMTYSHDN IICGITSVSF SKSGRLLLAG YDDFNCNVWD ALKADRAGVL AGHDNRVSCL GVT DDGMAV ATGSWDSFLK IWN |
-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: ![]() |
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 |
-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: 30.363043 KDa |
組換発現 | 生物種: ![]() ![]() |
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 GGGGSADIVM TQATSSVPVT PGESVSISCR SSKSLLHSNG NTYLYWFLQR PGQSPQLLIY RMSNLASGVP DR FSGSGSG TAFTLTISRL EAEDVGVYYC MQHLEYPLTF GAGTKLEL |
-分子 #4: Guanine nucleotide-binding protein G(q) subunit alpha
分子 | 名称: Guanine nucleotide-binding protein G(q) subunit alpha 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: 40.555199 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 FDVGAQRSER KKWIHCFEGV TAIIFCVALS DYDLVLAEDE EM NRMHESM KLFDSICNNK WFTDTSIILF LNKKDLFEEK IKKSPLTICY PEYAGSNTYE EAAAYIQCQF EDLNKRKDTK EIY THFTCS TDTENIRFVF AAVKDTILQL NLKEYNLV |
-分子 #5: Free fatty acid receptor 4
分子 | 名称: Free fatty acid receptor 4 / 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: 40.533211 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: MSPECARAAG DAPLRSLEQA NRTRFPFFSD VKGDHRLVLA AVETTVLVLI FAVSLLGNVC ALVLVARRRR RGATACLVLN LFCADLLFI SAIPLVLAVR WTEAWLLGPV ACHLLFYVMT LSGSVTILTL AAVSLERMVC IVHLQRGVRG PGRRARAVLL A LIWGYSAV ...文字列: MSPECARAAG DAPLRSLEQA NRTRFPFFSD VKGDHRLVLA AVETTVLVLI FAVSLLGNVC ALVLVARRRR RGATACLVLN LFCADLLFI SAIPLVLAVR WTEAWLLGPV ACHLLFYVMT LSGSVTILTL AAVSLERMVC IVHLQRGVRG PGRRARAVLL A LIWGYSAV AALPLCVFFR VVPQRLPGAD QEISICTLIW PTIPGEISWD VSFVTLNFLV PGLVIVISYS KILQITKASR KR LTVSLAY SESHQIRVSQ QDFRLFRTLF LLMVSFFIMW SPIIITILLI LIQNFKQDLV IWPSLFFWVV AFTFANSALN PIL YNMTLC RNEWKKIFCC FWFPEKGAIL TDTSVKRNDL SIISG |
-分子 #6: 3-{4-[(4-fluoro-4'-methyl[1,1'-biphenyl]-2-yl)methoxy]phenyl}prop...
分子 | 名称: 3-{4-[(4-fluoro-4'-methyl[1,1'-biphenyl]-2-yl)methoxy]phenyl}propanoic acid タイプ: ligand / ID: 6 / コピー数: 1 / 式: YN9 |
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分子量 | 理論値: 364.409 Da |
Chemical component information | ![]() ChemComp-YN9: |
-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: FEI FALCON IV (4k x 4k) 平均電子線量: 52.0 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): 2.0 µm / 最小 デフォーカス(公称値): 1.0 µm |
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |
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画像解析
最終 再構成 | 解像度のタイプ: BY AUTHOR / 解像度: 2.64 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 303739 |
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初期 角度割当 | タイプ: RANDOM ASSIGNMENT |
最終 角度割当 | タイプ: MAXIMUM LIKELIHOOD |