+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-30827 | |||||||||
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タイトル | Human Wntless in complex with Wnt3a | |||||||||
マップデータ | 2.2_angstrom_map for WLS-Wnt3a complex | |||||||||
試料 |
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機能・相同性 | 機能・相同性情報 Wnt signaling pathway involved in forebrain neuroblast division / positive regulation of dermatome development / axis elongation involved in somitogenesis / calcium ion transmembrane transport via low voltage-gated calcium channel / positive regulation of collateral sprouting in absence of injury / positive regulation of mesodermal cell fate specification / paraxial mesodermal cell fate commitment / cell proliferation in midbrain / spinal cord association neuron differentiation / Formation of the posterior neural plate ...Wnt signaling pathway involved in forebrain neuroblast division / positive regulation of dermatome development / axis elongation involved in somitogenesis / calcium ion transmembrane transport via low voltage-gated calcium channel / positive regulation of collateral sprouting in absence of injury / positive regulation of mesodermal cell fate specification / paraxial mesodermal cell fate commitment / cell proliferation in midbrain / spinal cord association neuron differentiation / Formation of the posterior neural plate / Wnt protein secretion / COP9 signalosome assembly / Wnt-Frizzled-LRP5/6 complex / positive regulation of Wnt protein secretion / positive regulation of cell-cell adhesion mediated by cadherin / Negative regulation of TCF-dependent signaling by WNT ligand antagonists / synaptic vesicle recycling / Signaling by RNF43 mutants / WNT ligand biogenesis and trafficking / positive regulation of cardiac muscle cell differentiation / cell proliferation in forebrain / negative regulation of axon extension involved in axon guidance / secondary palate development / Specification of the neural plate border / cementum mineralization / somatic stem cell division / non-canonical Wnt signaling pathway / co-receptor binding / cardiac muscle cell fate commitment / presynapse assembly / hindbrain development / positive regulation of skeletal muscle tissue development / Wnt-protein binding / negative regulation of dopaminergic neuron differentiation / midbrain dopaminergic neuron differentiation / dorsal/ventral neural tube patterning / regulation of postsynapse to nucleus signaling pathway / exocrine pancreas development / mammary gland development / post-anal tail morphogenesis / frizzled binding / positive regulation of neural precursor cell proliferation / positive regulation of hepatocyte proliferation / Class B/2 (Secretin family receptors) / Disassembly of the destruction complex and recruitment of AXIN to the membrane / myoblast differentiation / anterior/posterior axis specification / inner ear morphogenesis / midbrain development / organelle membrane / cell fate commitment / regulation of synapse organization / negative regulation of fat cell differentiation / B cell proliferation / fat cell differentiation / heart looping / Formation of paraxial mesoderm / skeletal muscle cell differentiation / positive regulation of receptor internalization / hemopoiesis / mesoderm formation / regulation of presynapse assembly / positive regulation of Wnt signaling pathway / Transcriptional and post-translational regulation of MITF-M expression and activity / canonical Wnt signaling pathway / endomembrane system / regulation of microtubule cytoskeleton organization / cellular response to retinoic acid / positive regulation of B cell proliferation / Regulation of FZD by ubiquitination / positive regulation of protein localization to plasma membrane / extracellular matrix organization / positive regulation of cytokine production / TCF dependent signaling in response to WNT / cytokine activity / axon guidance / hippocampus development / intracellular protein transport / trans-Golgi network / modulation of chemical synaptic transmission / neuron differentiation / Wnt signaling pathway / platelet aggregation / negative regulation of neurogenesis / Golgi lumen / osteoblast differentiation / positive regulation of canonical Wnt signaling pathway / endocytic vesicle membrane / positive regulation of peptidyl-serine phosphorylation / protein localization / negative regulation of neuron projection development / early endosome membrane / presynapse / heart development / positive regulation of canonical NF-kappaB signal transduction / cytoplasmic vesicle / transcription coactivator activity / in utero embryonic development / cell population proliferation / transcription by RNA polymerase II 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: 2.2 Å | |||||||||
データ登録者 | Zhong Q / Zhao Y / Ye F / Xiao Z / Huang G / Zhang Y / Lu P / Xu W / Zhou Q / Ma D | |||||||||
資金援助 | 中国, 1件
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引用 | ジャーナル: Nat Commun / 年: 2021 タイトル: Cryo-EM structure of human Wntless in complex with Wnt3a. 著者: Qing Zhong / Yanyu Zhao / Fangfei Ye / Zaiyu Xiao / Gaoxingyu Huang / Meng Xu / Yuanyuan Zhang / Xiechao Zhan / Ke Sun / Zhizhi Wang / Shanshan Cheng / Shan Feng / Xiuxiu Zhao / Jizhong Zhang ...著者: Qing Zhong / Yanyu Zhao / Fangfei Ye / Zaiyu Xiao / Gaoxingyu Huang / Meng Xu / Yuanyuan Zhang / Xiechao Zhan / Ke Sun / Zhizhi Wang / Shanshan Cheng / Shan Feng / Xiuxiu Zhao / Jizhong Zhang / Peilong Lu / Wenqing Xu / Qiang Zhou / Dan Ma / 要旨: Wntless (WLS), an evolutionarily conserved multi-pass transmembrane protein, is essential for secretion of Wnt proteins. Wnt-triggered signaling pathways control many crucial life events, whereas ...Wntless (WLS), an evolutionarily conserved multi-pass transmembrane protein, is essential for secretion of Wnt proteins. Wnt-triggered signaling pathways control many crucial life events, whereas aberrant Wnt signaling is tightly associated with many human diseases including cancers. Here, we report the cryo-EM structure of human WLS in complex with Wnt3a, the most widely studied Wnt, at 2.2 Å resolution. The transmembrane domain of WLS bears a GPCR fold, with a conserved core cavity and a lateral opening. Wnt3a interacts with WLS at multiple interfaces, with the lipid moiety on Wnt3a traversing a hydrophobic tunnel of WLS transmembrane domain and inserting into membrane. A β-hairpin of Wnt3a containing the conserved palmitoleoylation site interacts with WLS extensively, which is crucial for WLS-mediated Wnt secretion. The flexibility of the Wnt3a loop/hairpin regions involved in the multiple binding sites indicates induced fit might happen when Wnts are bound to different binding partners. Our findings provide important insights into the molecular mechanism of Wnt palmitoleoylation, secretion and signaling. | |||||||||
履歴 |
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-構造の表示
ムービー |
ムービービューア |
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構造ビューア | EMマップ: SurfViewMolmilJmol/JSmol |
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_30827.map.gz | 482.7 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-30827-v30.xml emd-30827.xml | 17.1 KB 17.1 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_30827.png | 60.5 KB | ||
その他 | emd_30827_additional_1.map.gz | 28.6 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-30827 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-30827 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_30827_validation.pdf.gz | 417.6 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_30827_full_validation.pdf.gz | 417.2 KB | 表示 | |
XML形式データ | emd_30827_validation.xml.gz | 7.8 KB | 表示 | |
CIF形式データ | emd_30827_validation.cif.gz | 8.9 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-30827 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-30827 | 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_30827.map.gz / 形式: CCP4 / 大きさ: 512 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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注釈 | 2.2_angstrom_map for WLS-Wnt3a complex | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 0.5435 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
CCP4マップ ヘッダ情報:
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-添付データ
-追加マップ: 3.2 angstrom map for WLS-Wnt3a complex
ファイル | emd_30827_additional_1.map | ||||||||||||
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注釈 | 3.2_angstrom_map for WLS-Wnt3a complex | ||||||||||||
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 : Human Wntless in complex with Wnt3a
+超分子 #1: Human Wntless in complex with Wnt3a
+超分子 #2: Wnt3a
+超分子 #3: Wntless
+分子 #1: Protein Wnt-3a
+分子 #2: Protein wntless homolog
+分子 #4: PALMITOLEIC ACID
+分子 #5: 1,2-DIOLEOYL-SN-GLYCERO-3-PHOSPHOCHOLINE
+分子 #6: CHOLESTEROL
+分子 #7: 1-O-OCTADECYL-SN-GLYCERO-3-PHOSPHOCHOLINE
+分子 #8: water
-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: 8 |
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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 BIOQUANTUM (6k x 4k) 平均電子線量: 50.0 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: FLOOD BEAM / 撮影モード: BRIGHT FIELD |
試料ステージ | 試料ホルダーモデル: FEI TITAN KRIOS AUTOGRID HOLDER ホルダー冷却材: NITROGEN |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
-画像解析
最終 再構成 | 解像度のタイプ: BY AUTHOR / 解像度: 2.2 Å / 解像度の算出法: FSC 0.143 CUT-OFF / ソフトウェア - 名称: RELION (ver. 3.0.6) / 使用した粒子像数: 8482332 |
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初期 角度割当 | タイプ: ANGULAR RECONSTITUTION |
最終 角度割当 | タイプ: MAXIMUM LIKELIHOOD |