+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 8tzo | ||||||||||||
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タイトル | Structure of human Wnt7a bound to WLS and CALR | ||||||||||||
要素 |
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キーワード | SIGNALING PROTEIN | ||||||||||||
機能・相同性 | 機能・相同性情報 postsynapse assembly / positive regulation of excitatory synapse assembly / regulation of axon diameter / positive regulation of protein localization to presynapse / skeletal muscle satellite cell activation / Wnt protein secretion / Calnexin/calreticulin cycle / asymmetric protein localization involved in cell fate determination / excitatory synapse assembly / cerebellar granule cell differentiation ...postsynapse assembly / positive regulation of excitatory synapse assembly / regulation of axon diameter / positive regulation of protein localization to presynapse / skeletal muscle satellite cell activation / Wnt protein secretion / Calnexin/calreticulin cycle / asymmetric protein localization involved in cell fate determination / excitatory synapse assembly / cerebellar granule cell differentiation / cytolytic granule / positive regulation of Wnt protein secretion / lens fiber cell development / synaptic vesicle recycling / positive regulation of dendritic cell chemotaxis / WNT ligand biogenesis and trafficking / oviduct development / cortical granule / Assembly of Viral Components at the Budding Site / negative regulation of trophoblast cell migration / ATF6 (ATF6-alpha) activates chaperone genes / central nervous system vasculogenesis / cell proliferation in forebrain / negative regulation of retinoic acid receptor signaling pathway / cellular response to electrical stimulus / endoplasmic reticulum quality control compartment / complement component C1q complex binding / uterus morphogenesis / nuclear receptor-mediated glucocorticoid signaling pathway / secondary palate development / skeletal muscle satellite cell maintenance involved in skeletal muscle regeneration / regulation of meiotic nuclear division / embryonic axis specification / cementum mineralization / response to glycoside / sequestering of calcium ion / somatic stem cell division / sarcoplasmic reticulum lumen / protein folding in endoplasmic reticulum / presynapse assembly / hormone binding / sex differentiation / positive regulation of epithelial cell proliferation involved in wound healing / hindbrain development / Wnt-protein binding / stem cell development / nuclear export signal receptor activity / negative regulation of intracellular steroid hormone receptor signaling pathway / establishment of blood-brain barrier / cardiac muscle cell differentiation / molecular sequestering activity / exocrine pancreas development / neurotransmitter secretion / frizzled binding / dendritic spine morphogenesis / dorsal/ventral pattern formation / embryonic forelimb morphogenesis / Class B/2 (Secretin family receptors) / embryonic hindlimb morphogenesis / positive regulation of synapse assembly / wound healing, spreading of epidermal cells / Wnt signaling pathway, planar cell polarity pathway / anterior/posterior axis specification / protein maturation by protein folding / Scavenging by Class F Receptors / Scavenging by Class A Receptors / regulation of postsynapse organization / cortical actin cytoskeleton organization / midbrain development / regulation of synaptic vesicle exocytosis / embryonic digit morphogenesis / cartilage condensation / nuclear androgen receptor binding / organelle membrane / establishment of cell polarity / cell fate commitment / cellular response to lithium ion / response to testosterone / somatic stem cell population maintenance / positive regulation of excitatory postsynaptic potential / mesoderm formation / regulation of presynapse assembly / protein localization to nucleus / positive regulation of Wnt signaling pathway / negative regulation of neuron differentiation / smooth endoplasmic reticulum / canonical Wnt signaling pathway / endomembrane system / chondrocyte differentiation / positive regulation of cell cycle / ERAD pathway / positive regulation of substrate adhesion-dependent cell spreading / positive regulation of phagocytosis / protein folding chaperone / cellular response to transforming growth factor beta stimulus / endocytic vesicle lumen / positive regulation of protein metabolic process / protein export from nucleus / positive regulation of endothelial cell migration / endoplasmic reticulum-Golgi intermediate compartment membrane 類似検索 - 分子機能 | ||||||||||||
生物種 | Homo sapiens (ヒト) | ||||||||||||
手法 | 電子顕微鏡法 / 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.1 Å | ||||||||||||
データ登録者 | Qi, X. / Hu, Q. / Li, X. | ||||||||||||
資金援助 | 米国, 3件
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引用 | ジャーナル: Cell / 年: 2023 タイトル: Molecular basis of Wnt biogenesis, secretion, and Wnt7-specific signaling. 著者: Xiaofeng Qi / Qinli Hu / Nadia Elghobashi-Meinhardt / Tao Long / Hongwen Chen / Xiaochun Li / 要旨: Wnt proteins are enzymatically lipidated by Porcupine (PORCN) in the ER and bind to Wntless (WLS) for intracellular transport and secretion. Mechanisms governing the transfer of these low-solubility ...Wnt proteins are enzymatically lipidated by Porcupine (PORCN) in the ER and bind to Wntless (WLS) for intracellular transport and secretion. Mechanisms governing the transfer of these low-solubility Wnts from the ER to the extracellular space remain unclear. Through structural and functional analyses of Wnt7a, a crucial Wnt involved in central nervous system angiogenesis and blood-brain barrier maintenance, we have elucidated the principles of Wnt biogenesis and Wnt7-specific signaling. The Wnt7a-WLS complex binds to calreticulin (CALR), revealing that CALR functions as a chaperone to facilitate Wnt transfer from PORCN to WLS during Wnt biogenesis. Our structures, functional analyses, and molecular dynamics simulations demonstrate that a phospholipid in the core of Wnt-bound WLS regulates the association and dissociation between Wnt and WLS, suggesting a lipid-mediated Wnt secretion mechanism. Finally, the structure of Wnt7a bound to RECK, a cell-surface Wnt7 co-receptor, reveals how RECK engages the N-terminal domain of Wnt7a to activate Wnt7-specific signaling. | ||||||||||||
履歴 |
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-構造の表示
構造ビューア | 分子: MolmilJmol/JSmol |
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-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 8tzo.cif.gz | 236.1 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb8tzo.ent.gz | 181.7 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 8tzo.json.gz | ツリー表示 | PDBx/mmJSON形式 | |
その他 | その他のダウンロード |
-検証レポート
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/tz/8tzo ftp://data.pdbj.org/pub/pdb/validation_reports/tz/8tzo | HTTPS FTP |
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-関連構造データ
関連構造データ | 41764MC 8tzpC 8tzsC M: このデータのモデリングに利用したマップデータ C: 同じ文献を引用 (文献) |
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類似構造データ | 類似検索 - 機能・相同性F&H 検索 |
-リンク
-集合体
登録構造単位 |
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1 |
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-要素
-タンパク質 , 3種, 3分子 ABC
#1: タンパク質 | 分子量: 39062.977 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: WNT7A / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: O00755 |
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#2: タンパク質 | 分子量: 62317.973 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: WLS / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: Q5T9L3 |
#3: タンパク質 | 分子量: 48198.379 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Homo sapiens (ヒト) / 参照: UniProt: P27797 |
-糖 , 1種, 1分子
#4: 多糖 | alpha-D-glucopyranose-(1-3)-alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-2)-alpha-D- ...alpha-D-glucopyranose-(1-3)-alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose タイプ: oligosaccharide / 分子量: 1235.105 Da / 分子数: 1 / 由来タイプ: 組換発現 |
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-非ポリマー , 3種, 3分子
#5: 化合物 | ChemComp-PAM / |
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#6: 化合物 | ChemComp-POV / ( |
#7: 化合物 | ChemComp-CA / |
-詳細
研究の焦点であるリガンドがあるか | Y |
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-実験情報
-実験
実験 | 手法: 電子顕微鏡法 |
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EM実験 | 試料の集合状態: PARTICLE / 3次元再構成法: 単粒子再構成法 |
-試料調製
構成要素 | 名称: Wnt7a-WLS-CALR Complex / タイプ: COMPLEX / Entity ID: #1-#3 / 由来: MULTIPLE SOURCES |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
由来(組換発現) | 生物種: Homo sapiens (ヒト) |
緩衝液 | pH: 7.5 |
試料 | 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES |
急速凍結 | 凍結剤: ETHANE |
-電子顕微鏡撮影
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
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顕微鏡 | モデル: FEI TITAN KRIOS |
電子銃 | 電子線源: FIELD EMISSION GUN / 加速電圧: 300 kV / 照射モード: FLOOD BEAM |
電子レンズ | モード: BRIGHT FIELD / 最大 デフォーカス(公称値): 2000 nm / 最小 デフォーカス(公称値): 1000 nm |
撮影 | 電子線照射量: 60 e/Å2 / フィルム・検出器のモデル: GATAN K3 (6k x 4k) |
-解析
CTF補正 | タイプ: NONE | ||||||||||||||||||||||||
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3次元再構成 | 解像度: 3.1 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 276377 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
拘束条件 |
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