+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-36111 | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
タイトル | Gq bound FZD1 in ligand-free state | |||||||||
マップデータ | ||||||||||
試料 |
| |||||||||
キーワード | FZD1-Gq / class-F / Frizzled receptor / Complex / MEMBRANE PROTEIN | |||||||||
機能・相同性 | 機能・相同性情報 muscular septum morphogenesis / regulation of mesenchymal stem cell differentiation / autocrine signaling / : / astrocyte-dopaminergic neuron signaling / canonical Wnt signaling pathway involved in mesenchymal stem cell differentiation / hard palate development / Fatty Acids bound to GPR40 (FFAR1) regulate insulin secretion / Acetylcholine regulates insulin secretion / Wnt receptor activity ...muscular septum morphogenesis / regulation of mesenchymal stem cell differentiation / autocrine signaling / : / astrocyte-dopaminergic neuron signaling / canonical Wnt signaling pathway involved in mesenchymal stem cell differentiation / hard palate development / Fatty Acids bound to GPR40 (FFAR1) regulate insulin secretion / Acetylcholine regulates insulin secretion / Wnt receptor activity / non-canonical Wnt signaling pathway / membranous septum morphogenesis / presynapse assembly / PLC beta mediated events / Wnt-protein binding / phospholipase C-activating dopamine receptor signaling pathway / endothelial cell differentiation / entrainment of circadian clock / midbrain dopaminergic neuron differentiation / regulation of platelet activation / phototransduction, visible light / negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway / frizzled binding / glutamate receptor signaling pathway / PCP/CE pathway / Wnt signalosome / Class B/2 (Secretin family receptors) / : / regulation of canonical Wnt signaling pathway / Disassembly of the destruction complex and recruitment of AXIN to the membrane / negative regulation of BMP signaling pathway / outflow tract morphogenesis / action potential / PKA activation in glucagon signalling / hair follicle placode formation / regulation of presynapse assembly / photoreceptor outer segment / developmental growth / D1 dopamine receptor binding / intracellular transport / canonical Wnt signaling pathway / Hedgehog 'off' state / positive regulation of osteoblast differentiation / adenylate cyclase-activating adrenergic receptor signaling pathway / activation of adenylate cyclase activity / adenylate cyclase activator activity / GTPase activator activity / trans-Golgi network membrane / Asymmetric localization of PCP proteins / TCF dependent signaling in response to WNT / G protein-coupled receptor binding / PDZ domain binding / G protein-coupled receptor activity / negative regulation of protein kinase activity / positive regulation of DNA-binding transcription factor activity / G-protein beta/gamma-subunit complex binding / bone development / Olfactory Signaling Pathway / negative regulation of canonical Wnt 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 / neuron differentiation / 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 / positive regulation of neuron projection development / 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 / blood coagulation / extracellular vesicle 類似検索 - 分子機能 | |||||||||
生物種 | Homo sapiens (ヒト) / Vicugna pacos (アルパカ) | |||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.5 Å | |||||||||
データ登録者 | Lin X / Xu F | |||||||||
資金援助 | 1件
| |||||||||
引用 | ジャーナル: Cell Discov / 年: 2024 タイトル: A framework for Frizzled-G protein coupling and implications to the PCP signaling pathways. 著者: Zhibin Zhang / Xi Lin / Ling Wei / Yiran Wu / Lu Xu / Lijie Wu / Xiaohu Wei / Suwen Zhao / Xiangjia Zhu / Fei Xu / 要旨: The ten Frizzled receptors (FZDs) are essential in Wnt signaling and play important roles in embryonic development and tumorigenesis. Among these, FZD6 is closely associated with lens development. ...The ten Frizzled receptors (FZDs) are essential in Wnt signaling and play important roles in embryonic development and tumorigenesis. Among these, FZD6 is closely associated with lens development. Understanding FZD activation mechanism is key to unlock these emerging targets. Here we present the cryo-EM structures of FZD6 and FZD3 which are known to relay non-canonical planar cell polarity (PCP) signaling pathways as well as FZD1 in their G protein-coupled states and in the apo inactive states, respectively. Comparison of the three inactive/active pairs unveiled a shared activation framework among all ten FZDs. Mutagenesis along with imaging and functional analysis on the human lens epithelial tissues suggested potential crosstalk between the G-protein coupling of FZD6 and the PCP signaling pathways. Together, this study provides an integrated understanding of FZD structure and function, and lays the foundation for developing therapeutic modulators to activate or inhibit FZD signaling for a range of disorders including cancers and cataracts. | |||||||||
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 | emd_36111.map.gz | 49.3 MB | EMDBマップデータ形式 | |
---|---|---|---|---|
ヘッダ (付随情報) | emd-36111-v30.xml emd-36111.xml | 20.7 KB 20.7 KB | 表示 表示 | EMDBヘッダ |
FSC (解像度算出) | emd_36111_fsc.xml | 8.1 KB | 表示 | FSCデータファイル |
画像 | emd_36111.png | 33.6 KB | ||
Filedesc metadata | emd-36111.cif.gz | 6.5 KB | ||
その他 | emd_36111_additional_1.map.gz emd_36111_half_map_1.map.gz emd_36111_half_map_2.map.gz | 52.3 MB 51.5 MB 51.5 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-36111 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-36111 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_36111_validation.pdf.gz | 764.7 KB | 表示 | EMDB検証レポート |
---|---|---|---|---|
文書・詳細版 | emd_36111_full_validation.pdf.gz | 764.2 KB | 表示 | |
XML形式データ | emd_36111_validation.xml.gz | 15.6 KB | 表示 | |
CIF形式データ | emd_36111_validation.cif.gz | 20.4 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-36111 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-36111 | HTTPS FTP |
-関連構造データ
-リンク
EMDBのページ | EMDB (EBI/PDBe) / EMDataResource |
---|---|
「今月の分子」の関連する項目 |
-マップ
ファイル | ダウンロード / ファイル: emd_36111.map.gz / 形式: CCP4 / 大きさ: 55.4 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
ボクセルのサイズ | X=Y=Z: 1.06 Å | ||||||||||||||||||||
密度 |
| ||||||||||||||||||||
対称性 | 空間群: 1 | ||||||||||||||||||||
詳細 | EMDB XML:
|
-添付データ
-追加マップ: #1
ファイル | emd_36111_additional_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_36111_half_map_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
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_36111_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 : FZD1-Gq complex in the ligand-free state
全体 | 名称: FZD1-Gq complex in the ligand-free state |
---|---|
要素 |
|
-超分子 #1: FZD1-Gq complex in the ligand-free state
超分子 | 名称: FZD1-Gq complex in the ligand-free state / タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: all |
---|---|
由来(天然) | 生物種: Homo sapiens (ヒト) |
-分子 #1: Frizzled-1
分子 | 名称: Frizzled-1 / 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: Homo sapiens (ヒト) |
分子量 | 理論値: 64.015668 KDa |
組換発現 | 生物種: Spodoptera frugiperda (ツマジロクサヨトウ) |
配列 | 文字列: GVRAQAAGQG PGQGPGPGQQ PPPPPQQQQS GQQYNGERGI SVPDHGYCQP ISIPLCTDIA YNQTIMPNLL GHTNQEDAGL EVHQFYPLV KVQCSAELKF FLCSMYAPVC TVLEQALPPC RSLCERARQG CEALMNKFGF QWPDTLKCEK FPVHGAGELC V GQNTSDKG ...文字列: GVRAQAAGQG PGQGPGPGQQ PPPPPQQQQS GQQYNGERGI SVPDHGYCQP ISIPLCTDIA YNQTIMPNLL GHTNQEDAGL EVHQFYPLV KVQCSAELKF FLCSMYAPVC TVLEQALPPC RSLCERARQG CEALMNKFGF QWPDTLKCEK FPVHGAGELC V GQNTSDKG TPTPSLLPEF WTSNPQHGGG GHRGGFPGGA GASERGKFSC PRALKVPSYL NYHFLGEKDC GAPCEPTKVY GL MYFGPEE LRFSRTWIGI WSVLCCASTL FTVLTYLVDM RRFSYPERPI IFLSGCYTAV AVAYIAGFLL EDRVVCNDKF AED GARTVA QGTKKEGCTI LFMMLYFFSM ASSIWWVILS LTWFLAAGMK WGHEAIEANS QYFHLAAWAV PAIKTITILA LGQV DGDVL SGVCFVGLNN VDALRGFVLA PLFVYLFIGT SFLLAGFVSL FRIRTIMKHD GTKTEKLEKL MVRIGVFSVL YTVPA TIVI ACYFYEQAFR DQWERSWVAQ SCKSYAIPCP HLQAGGGAPP HPPMSPDFTV FMIKYLMTLI VGITSGFWIW SGKTLN SWR KFYTRLTNSK QGETTV UniProtKB: Frizzled-1 |
-分子 #2: Guanine nucleotide-binding protein G(s) subunit alpha isoforms sh...
分子 | 名称: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short,Guanine nucleotide-binding protein G(q) subunit alpha タイプ: protein_or_peptide / ID: 2 / 詳細: Chimeric protein MiniGQ / コピー数: 1 / 光学異性体: LEVO |
---|---|
由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 28.8205 KDa |
組換発現 | 生物種: Escherichia coli (大腸菌) |
配列 | 文字列: GNSKTEDQRN EEKAQREANK KIEQLRRDKR DARRATHRLL LLGADNSGKS TIVKQMRILH GGSGGSGGTS GIFETKFQVD KVNFHMFDV GGQRDERRKW IQCFNDVTAI IFVVDSSDYN RLQEALNLFK SIWNNRWLRT ISVILFLNKQ DLLAEKVLAG K SKIEDYFP ...文字列: GNSKTEDQRN EEKAQREANK KIEQLRRDKR DARRATHRLL LLGADNSGKS TIVKQMRILH GGSGGSGGTS GIFETKFQVD KVNFHMFDV GGQRDERRKW IQCFNDVTAI IFVVDSSDYN RLQEALNLFK SIWNNRWLRT ISVILFLNKQ DLLAEKVLAG K SKIEDYFP EFARYTTPED ATPEPGEDPR VTRAKYFIRD EFLRISTASG DGRHYCYPHF TCAVDTENAR RIFNDCKDTI LQ LNLKEYN LV UniProtKB: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short, Guanine nucleotide-binding protein G(q) subunit alpha, Guanine nucleotide-binding protein G(s) subunit alpha isoforms ...UniProtKB: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short, Guanine nucleotide-binding protein G(q) subunit alpha, Guanine nucleotide-binding protein G(s) subunit alpha isoforms short, Guanine nucleotide-binding protein G(s) subunit alpha isoforms short, Guanine nucleotide-binding protein G(q) subunit alpha |
-分子 #3: 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: 3 / コピー数: 1 / 光学異性体: LEVO |
---|---|
由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 37.41693 KDa |
組換発現 | 生物種: Trichoplusia ni (イラクサキンウワバ) |
配列 | 文字列: MSELDQLRQE AEQLKNQIRD ARKACADATL SQITNNIDPV GRIQMRTRRT LRGHLAKIYA MHWGTDSRLL VSASQDGKLI IWDSYTTNK VHAIPLRSSW VMTCAYAPSG NYVACGGLDN ICSIYNLKTR EGNVRVSREL AGHTGYLSCC RFLDDNQIVT S SGDTTCAL ...文字列: MSELDQLRQE AEQLKNQIRD ARKACADATL SQITNNIDPV GRIQMRTRRT LRGHLAKIYA MHWGTDSRLL VSASQDGKLI IWDSYTTNK VHAIPLRSSW VMTCAYAPSG NYVACGGLDN ICSIYNLKTR EGNVRVSREL AGHTGYLSCC RFLDDNQIVT S SGDTTCAL WDIETGQQTT TFTGHTGDVM SLSLAPDTRL FVSGACDASA KLWDVREGMC RQTFTGHESD INAICFFPNG NA FATGSDD ATCRLFDLRA DQELMTYSHD NIICGITSVS FSKSGRLLLA GYDDFNCNVW DALKADRAGV LAGHDNRVSC LGV TDDGMA VATGSWDSFL KIWN UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 |
-分子 #4: 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: 4 / コピー数: 1 / 光学異性体: LEVO |
---|---|
由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 7.845078 KDa |
組換発現 | 生物種: Trichoplusia ni (イラクサキンウワバ) |
配列 | 文字列: MASNNTASIA QARKLVEQLK MEANIDRIKV SKAAADLMAY CEAHAKEDPL LTPVPASENP FREKKFFSAI L UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 |
-分子 #5: nanobody Nb35
分子 | 名称: nanobody Nb35 / 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: Vicugna pacos (アルパカ) |
分子量 | 理論値: 16.054232 KDa |
組換発現 | 生物種: Escherichia coli (大腸菌) |
配列 | 文字列: MKYLLPTAAA GLLLLAAQPA MAMQVQLQES GGGLVQPGGS LRLSCAASGF TFSNYKMNWV RQAPGKGLEW VSDISQSGAS ISYTGSVKG RFTISRDNAK NTLYLQMNSL KPEDTAVYYC ARCPAPFTRD CFDVTSTTYA YRGQGTQVTV |
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
---|---|
解析 | 単粒子再構成法 |
試料の集合状態 | particle |
-試料調製
緩衝液 | pH: 7.5 |
---|---|
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: 60.0 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: OTHER |
電子光学系 | 照射モード: OTHER / 撮影モード: OTHER / 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): 0.7000000000000001 µm |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |