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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 C16:0 ceramide-bound FPR2-Gi complex | |||||||||
マップデータ | ||||||||||
試料 |
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キーワード | MEMBRANE PROTEIN | |||||||||
| 機能・相同性 | 機能・相同性情報N-formyl peptide receptor activity / complement receptor activity / immune response-regulating cell surface receptor signaling pathway / scavenger receptor binding / RAGE receptor binding / complement receptor mediated signaling pathway / positive regulation of monocyte chemotaxis / positive regulation of innate immune response / Formyl peptide receptors bind formyl peptides and many other ligands / cargo receptor activity ...N-formyl peptide receptor activity / complement receptor activity / immune response-regulating cell surface receptor signaling pathway / scavenger receptor binding / RAGE receptor binding / complement receptor mediated signaling pathway / positive regulation of monocyte chemotaxis / positive regulation of innate immune response / Formyl peptide receptors bind formyl peptides and many other ligands / cargo receptor activity / positive chemotaxis / tertiary granule membrane / ficolin-1-rich granule membrane / adenylate cyclase inhibitor activity / specific granule membrane / positive regulation of protein localization to cell cortex / positive regulation of superoxide anion generation / T cell migration / Adenylate cyclase inhibitory pathway / D2 dopamine receptor binding / response to prostaglandin E / adenylate cyclase regulator activity / G protein-coupled serotonin receptor binding / adenylate cyclase-inhibiting serotonin receptor signaling pathway / astrocyte activation / cellular response to forskolin / receptor-mediated endocytosis / positive regulation of phagocytosis / regulation of mitotic spindle organization / Regulation of insulin secretion / calcium-mediated signaling / positive regulation of cholesterol biosynthetic process / microglial cell activation / negative regulation of insulin secretion / G protein-coupled receptor binding / G protein-coupled receptor activity / response to peptide hormone / adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway / negative regulation of inflammatory response / adenylate cyclase-modulating G protein-coupled receptor signaling pathway / centriolar satellite / G-protein beta/gamma-subunit complex binding / 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 / cellular response to amyloid-beta / 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 / chemotaxis / 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 / photoreceptor disc membrane / Sensory perception of sweet, bitter, and umami (glutamate) taste / Glucagon-type ligand receptors / Adrenaline,noradrenaline inhibits insulin secretion / Vasopressin regulates renal water homeostasis via Aquaporins / GDP binding / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / G alpha (z) signalling events / cellular response to catecholamine stimulus / ADORA2B mediated anti-inflammatory cytokines production / ADP signalling through P2Y purinoceptor 1 / G beta:gamma signalling through PI3Kgamma / adenylate cyclase-activating dopamine receptor signaling pathway / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / 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 / signaling receptor activity / extracellular vesicle / signaling receptor complex adaptor activity / Thrombin signalling through proteinase activated receptors (PARs) / amyloid-beta binding / retina development in camera-type eye / G protein activity / positive regulation of cytosolic calcium ion concentration / GTPase binding / Ca2+ pathway / fibroblast proliferation / midbody / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / cell cortex / 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 / negative regulation of neuron apoptotic process 類似検索 - 分子機能 | |||||||||
| 生物種 | Homo sapiens (ヒト) / synthetic construct (人工物) | |||||||||
| 手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.2 Å | |||||||||
データ登録者 | Sun JP / Jiang CT / Kong W / Yu X / Cai K / Guo LL | |||||||||
| 資金援助 | 中国, 1件
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引用 | ジャーナル: Science / 年: 2025タイトル: Metabolic signaling of ceramides through the FPR2 receptor inhibits adipocyte thermogenesis. 著者: Hui Lin / Chuanshun Ma / Kui Cai / Lulu Guo / Xuemei Wang / Lin Lv / Chao Zhang / Jun Lin / Daolai Zhang / Chuan Ye / Tengwei Wang / Shenming Huang / Jifei Han / Zihao Zhang / Junyan Gao / ...著者: Hui Lin / Chuanshun Ma / Kui Cai / Lulu Guo / Xuemei Wang / Lin Lv / Chao Zhang / Jun Lin / Daolai Zhang / Chuan Ye / Tengwei Wang / Shenming Huang / Jifei Han / Zihao Zhang / Junyan Gao / Mingxiang Zhang / Zhao Pu / Fengyang Li / Yongyuan Guo / Xiaojun Zhou / Chengxue Qin / Fan Yi / Xiao Yu / Wei Kong / Changtao Jiang / Jin-Peng Sun / ![]() 要旨: Ceramides play a central role in human health and disease, yet their role as systemic signaling molecules remain poorly understood. In this work, we identify formyl peptide receptor 2 (FPR2) as a ...Ceramides play a central role in human health and disease, yet their role as systemic signaling molecules remain poorly understood. In this work, we identify formyl peptide receptor 2 (FPR2) as a membrane receptor that specifically binds long-chain ceramides (C14 to C20). In brown and beige adipocytes, C16:0 ceramide binding to FPR2 inhibits thermogenesis through G cyclic adenosine monophosphate signaling pathways, an effect that is reversed in the absence of FPR2. We present three cryo-electron microscopy structures of FPR2 in complex with G trimers bound to C16:0, C18:0, and C20:0 ceramides. The hydrophobic tails are deeply embedded in the orthosteric ligand pocket, which has a limited amount of plasticity. Modification of the ceramide binding motif in closely related receptors, such as FPR1 or FPR3, converts them from inactive to active ceramide receptors. Our findings provide a structural basis for adipocyte thermogenesis mediated by FPR2. | |||||||||
| 履歴 |
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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_38964.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-38964-v30.xml emd-38964.xml | 25.3 KB 25.3 KB | 表示 表示 | EMDBヘッダ |
| 画像 | emd_38964.png | 36.6 KB | ||
| Filedesc metadata | emd-38964.cif.gz | 7.6 KB | ||
| その他 | emd_38964_half_map_1.map.gz emd_38964_half_map_2.map.gz | 28.3 MB 28.3 MB | ||
| アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-38964 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-38964 | 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_38964.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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| 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: 1.06 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
-ハーフマップ: #2
| ファイル | emd_38964_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_38964_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 : Cryo-EM structure of the C16:0 ceramide-bound FPR2-Gi complex
| 全体 | 名称: Cryo-EM structure of the C16:0 ceramide-bound FPR2-Gi complex |
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| 要素 |
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-超分子 #1: Cryo-EM structure of the C16:0 ceramide-bound FPR2-Gi complex
| 超分子 | 名称: Cryo-EM structure of the C16:0 ceramide-bound FPR2-Gi complex 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) |
-分子 #1: 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: 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: 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 #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: Homo sapiens (ヒト) |
| 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 |
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| 由来(天然) | 生物種: Homo sapiens (ヒト) |
| 分子量 | 理論値: 6.504446 KDa |
| 組換発現 | 生物種: ![]() |
| 配列 | 文字列: NTASIAQARK LVEQLKMEAN IDRIKVSKAA ADLMAYCEAH AKEDPLLTPV PASENPFRE UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 |
-分子 #4: scFv16
| 分子 | 名称: scFv16 / 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: 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 #5: N-formyl peptide receptor 2
| 分子 | 名称: N-formyl peptide receptor 2 / 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: 38.993055 KDa |
| 組換発現 | 生物種: ![]() |
| 配列 | 文字列: METNFSTPLN EYEEVSYESA GYTVLRILPL VVLGVTFVLG VLGNGLVIWV AGFRMTRTVT TICYLNLALA DFSFTATLPF LIVSMAMGE KWPFGWFLCK LIHIVVDINL FGSVFLIGFI ALDRCICVLH PVWAQNHRTV SLAMKVIVGP WILALVLTLP V FLFLTTVT ...文字列: METNFSTPLN EYEEVSYESA GYTVLRILPL VVLGVTFVLG VLGNGLVIWV AGFRMTRTVT TICYLNLALA DFSFTATLPF LIVSMAMGE KWPFGWFLCK LIHIVVDINL FGSVFLIGFI ALDRCICVLH PVWAQNHRTV SLAMKVIVGP WILALVLTLP V FLFLTTVT IPNGDTYCTF NFASWGGTPE ERLKVAITML TARGIIRFVI GFSLPMSIVA ICYGLIAAKI HKKGMIKSSR PL RVLTAVV ASFFICWFPF QLVALLGTVW LKEMLFYGKY KIIDILVNPT SSLAFFNSCL NPMLYVFVGQ DFRERLIHSL PTS LERALS EDSAPTNDTA ANSASPPAET ELQAM UniProtKB: N-formyl peptide receptor 2 |
-分子 #6: N-((E,2S,3R)-1,3-DIHYDROXYOCTADEC-4-EN-2-YL)PALMITAMIDE
| 分子 | 名称: N-((E,2S,3R)-1,3-DIHYDROXYOCTADEC-4-EN-2-YL)PALMITAMIDE タイプ: ligand / ID: 6 / コピー数: 1 / 式: 16C |
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| 分子量 | 理論値: 537.901 Da |
| Chemical component information | ![]() ChemComp-16C: |
-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: 1.875 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: DIFFRACTION / 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): 0.6 µm |
| 実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |
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コントローラー
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



































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解析
FIELD EMISSION GUN

