+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-36261 | |||||||||
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タイトル | FZD6 Gs complex | |||||||||
マップデータ | ||||||||||
試料 |
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キーワード | FZD6 / Complex. / MEMBRANE PROTEIN | |||||||||
機能・相同性 | 機能・相同性情報 embryonic nail plate morphogenesis / establishment of body hair planar orientation / cell proliferation in midbrain / Signaling by RNF43 mutants / PKA activation in glucagon signalling / Wnt receptor activity / midbrain morphogenesis / non-canonical Wnt signaling pathway / sensory perception of chemical stimulus / Wnt-protein binding ...embryonic nail plate morphogenesis / establishment of body hair planar orientation / cell proliferation in midbrain / Signaling by RNF43 mutants / PKA activation in glucagon signalling / Wnt receptor activity / midbrain morphogenesis / non-canonical Wnt signaling pathway / sensory perception of chemical stimulus / Wnt-protein binding / mu-type opioid receptor binding / apicolateral plasma membrane / developmental growth / corticotropin-releasing hormone receptor 1 binding / D1 dopamine receptor binding / Hedgehog 'off' state / PCP/CE pathway / Class B/2 (Secretin family receptors) / Wnt signaling pathway, planar cell polarity pathway / beta-2 adrenergic receptor binding / inner ear morphogenesis / adenylate cyclase activator activity / hair follicle development / canonical Wnt signaling pathway / insulin-like growth factor receptor binding / ionotropic glutamate receptor binding / Regulation of FZD by ubiquitination / bone development / G-protein beta/gamma-subunit complex binding / platelet aggregation / neural tube closure / G protein-coupled receptor activity / adenylate cyclase-activating G protein-coupled receptor signaling pathway / cytoplasmic vesicle membrane / negative regulation of canonical Wnt signaling pathway / negative regulation of DNA-binding transcription factor activity / Olfactory Signaling Pathway / Activation of the phototransduction cascade / Prostacyclin signalling through prostacyclin receptor / G beta:gamma signalling through PLC beta / Presynaptic function of Kainate receptors / Thromboxane signalling through TP receptor / Glucagon signaling in metabolic regulation / G protein-coupled acetylcholine receptor signaling pathway / G-protein activation / platelet activation / Activation of G protein gated Potassium channels / Inhibition of voltage gated Ca2+ channels via Gbeta/gamma subunits / G beta:gamma signalling through CDC42 / Vasopressin regulates renal water homeostasis via Aquaporins / G beta:gamma signalling through BTK / ADP signalling through P2Y purinoceptor 12 / Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) / Glucagon-type ligand receptors / Sensory perception of sweet, bitter, and umami (glutamate) taste / photoreceptor disc membrane / G alpha (z) signalling events / Adrenaline,noradrenaline inhibits insulin secretion / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / ADORA2B mediated anti-inflammatory cytokines production / cellular response to catecholamine stimulus / sensory perception of taste / ADP signalling through P2Y purinoceptor 1 / adenylate cyclase-activating dopamine receptor signaling pathway / G beta:gamma signalling through PI3Kgamma / GPER1 signaling / Cooperation of PDCL (PhLP1) and TRiC/CCT in G-protein beta folding / cellular response to prostaglandin E stimulus / Inactivation, recovery and regulation of the phototransduction cascade / G-protein beta-subunit binding / heterotrimeric G-protein complex / positive regulation of cold-induced thermogenesis / G alpha (12/13) signalling events / extracellular vesicle / signaling receptor complex adaptor activity / 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 / Thrombin signalling through proteinase activated receptors (PARs) / GTPase binding / retina development in camera-type eye / Ca2+ pathway / phospholipase C-activating G protein-coupled receptor signaling pathway / G alpha (i) signalling events / fibroblast proliferation / G alpha (s) signalling events / G alpha (q) signalling events / Ras protein signal transduction / cell population proliferation / Extra-nuclear estrogen signaling / G protein-coupled receptor signaling pathway / apical plasma membrane / lysosomal membrane / GTPase activity / ubiquitin protein ligase binding / synapse / endoplasmic reticulum membrane / GTP binding / protein-containing complex binding / cell surface / signal transduction / extracellular exosome 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: 3.3 Å | |||||||||
データ登録者 | Xu F / Zhang Z | |||||||||
資金援助 | 1件
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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 |
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-構造の表示
添付画像 |
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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_36261.map.gz | 80.1 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-36261-v30.xml emd-36261.xml | 20.4 KB 20.4 KB | 表示 表示 | EMDBヘッダ |
FSC (解像度算出) | emd_36261_fsc.xml | 10.8 KB | 表示 | FSCデータファイル |
画像 | emd_36261.png | 44.7 KB | ||
Filedesc metadata | emd-36261.cif.gz | 6.3 KB | ||
その他 | emd_36261_additional_1.map.gz emd_36261_half_map_1.map.gz emd_36261_half_map_2.map.gz | 45.1 MB 84.7 MB 84.7 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-36261 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-36261 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_36261_validation.pdf.gz | 873.5 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_36261_full_validation.pdf.gz | 873.1 KB | 表示 | |
XML形式データ | emd_36261_validation.xml.gz | 17.8 KB | 表示 | |
CIF形式データ | emd_36261_validation.cif.gz | 22.9 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-36261 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-36261 | HTTPS FTP |
-関連構造データ
-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 |
-マップ
ファイル | ダウンロード / ファイル: emd_36261.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: 0.832 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
-追加マップ: #1
ファイル | emd_36261_additional_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_36261_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: #2
ファイル | emd_36261_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 |
-試料の構成要素
-全体 : FZD6-Gs complex with Nb35.
全体 | 名称: FZD6-Gs complex with Nb35. |
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要素 |
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-超分子 #1: FZD6-Gs complex with Nb35.
超分子 | 名称: FZD6-Gs complex with Nb35. / タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: all |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
-分子 #1: Guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas
分子 | 名称: Guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas タイプ: protein_or_peptide / ID: 1 / 詳細: minGas / 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: 31.117201 KDa |
組換発現 | 生物種: Escherichia coli (大腸菌) |
配列 | 文字列: HHHHHHENLY FQGSKTEDKR AQKRAEKKRS KLIDKQLQDE KMGYMCTHRL LLLGADNSGK STIVKQMRIL HGGSGGSGGT SGIFETKFQ VDKVNFHMFD VGGQRDERRK WIQCFNDVTA IIFVVDSSDY GSGGSGAGSA NRLQEALNLF KSIWNNRWLR T ISVILFLN ...文字列: HHHHHHENLY FQGSKTEDKR AQKRAEKKRS KLIDKQLQDE KMGYMCTHRL LLLGADNSGK STIVKQMRIL HGGSGGSGGT SGIFETKFQ VDKVNFHMFD VGGQRDERRK WIQCFNDVTA IIFVVDSSDY GSGGSGAGSA NRLQEALNLF KSIWNNRWLR T ISVILFLN KQDLLAEKVL AGKSKIEDYF PEFARYTTPE DATPEPGEDP RVTRAKYFIR DEFLRISTAS GDGRHYCYPH FT CAVDTEN ARRIFNDCRD IIQRMHLRQY ELL UniProtKB: Guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas, Guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas, Guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas |
-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: 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 #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: 8.417766 KDa |
組換発現 | 生物種: Trichoplusia ni (イラクサキンウワバ) |
配列 | 文字列: MHHHHHHNTA SIAQARKLVE QLKMEANIDR IKVSKAAADL MAYCEAHAKE DPLLTPVPAS ENPFREKKFF CAIL UniProtKB: Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 |
-分子 #4: Nb35
分子 | 名称: Nb35 / 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: 14.845516 KDa |
組換発現 | 生物種: Escherichia coli (大腸菌) |
配列 | 文字列: MQVQLQESGG GLVQPGGSLR LSCAASGFTF SNYKMNWVRQ APGKGLEWVS DISQSGASIS YTGSVKGRFT ISRDNAKNTL YLQMNSLKP EDTAVYYCAR CPAPFTRDCF DVTSTTYAYR GQGTQVTVSS HHHHHH |
-分子 #5: Frizzled-6
分子 | 名称: Frizzled-6 / 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: 61.912398 KDa |
組換発現 | 生物種: Spodoptera frugiperda (ツマジロクサヨトウ) |
配列 | 文字列: MKTIIALSYI FCLVFADYKD DDDKHHHHHH HSLFTCEPIT VPRCMKMAYN MTFFPNLMGH YDQSIAAVEM EHFLPLANLE CSPNIETFL CKAFVPTCIE QIHVVPPCRK LCEKVYSDCK KLIDTFGIRW PEELECDRLQ YCDETVPVTF DPHTEFLGPQ K KTEQVQRD ...文字列: MKTIIALSYI FCLVFADYKD DDDKHHHHHH HSLFTCEPIT VPRCMKMAYN MTFFPNLMGH YDQSIAAVEM EHFLPLANLE CSPNIETFL CKAFVPTCIE QIHVVPPCRK LCEKVYSDCK KLIDTFGIRW PEELECDRLQ YCDETVPVTF DPHTEFLGPQ K KTEQVQRD IGFWCPRHLK TSGGQGYKFL GIDQCAPPCP NMYFKSDELE FAKSFIGTVS IFCLCATLFT FLTFLIDVRR FR YPERPII YYSVCYSIVS LMYFIGFLLG DSTACNKADE KLELGDTVVL GSQNKACTVL FMLLYFFTMA GTVWWVILTI TWF LAAGRK WSCEAIEQKA VWFHAVAWGT PGFLTVMLLA MNKVEGDNIS GVCFVGLYDL DASRYFVLLP LCLCVFVGLS LLLA GIISL NHVRQVIQHD GRNQEKLKKF MIRIGVFSGL YLVPLVTLLG CYVYEQVNRI TWEITWVSDH CRQYHIPCPY QAKAK ARPE LALFMIKYLM TLIVGISAVF WVGSKKTCTE WAGFFKRNRK RDPISESRRV LQE UniProtKB: Frizzled-6 |
-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 |
-試料調製
緩衝液 | pH: 7.4 |
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凍結 | 凍結剤: ETHANE |
-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: 20.0 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: OTHER / 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): 1.2 µm |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |