+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-41765 | ||||||||||||
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タイトル | Structure of human Wnt7a bound to WLS and RECK | ||||||||||||
マップデータ | |||||||||||||
試料 |
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キーワード | SIGNALING PROTEIN | ||||||||||||
機能・相同性 | 機能・相同性情報 regulation of establishment of blood-brain barrier / : / postsynapse assembly / negative regulation of metalloendopeptidase activity / 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 / asymmetric protein localization involved in cell fate determination ...regulation of establishment of blood-brain barrier / : / postsynapse assembly / negative regulation of metalloendopeptidase activity / 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 / asymmetric protein localization involved in cell fate determination / excitatory synapse assembly / cerebellar granule cell differentiation / blood vessel maturation / positive regulation of Wnt protein secretion / lens fiber cell development / synaptic vesicle recycling / WNT ligand biogenesis and trafficking / oviduct development / central nervous system vasculogenesis / cell proliferation in forebrain / uterus morphogenesis / secondary palate development / skeletal muscle satellite cell maintenance involved in skeletal muscle regeneration / embryonic axis specification / Post-translational modification: synthesis of GPI-anchored proteins / cementum mineralization / metalloendopeptidase inhibitor activity / somatic stem cell division / presynapse assembly / sex differentiation / positive regulation of epithelial cell proliferation involved in wound healing / hindbrain development / Wnt-protein binding / stem cell development / establishment of blood-brain barrier / exocrine pancreas development / neurotransmitter secretion / frizzled binding / dendritic spine morphogenesis / dorsal/ventral pattern formation / embryonic forelimb morphogenesis / Wnt signalosome / Class B/2 (Secretin family receptors) / embryonic hindlimb morphogenesis / positive regulation of synapse assembly / wound healing, spreading of epidermal cells / sprouting angiogenesis / Wnt signaling pathway, planar cell polarity pathway / anterior/posterior axis specification / regulation of postsynapse organization / midbrain development / regulation of synaptic vesicle exocytosis / embryonic digit morphogenesis / cartilage condensation / endopeptidase inhibitor activity / organelle membrane / establishment of cell polarity / cell fate commitment / somatic stem cell population maintenance / positive regulation of excitatory postsynaptic potential / mesoderm formation / regulation of presynapse assembly / positive regulation of Wnt signaling pathway / canonical Wnt signaling pathway / endomembrane system / regulation of angiogenesis / chondrocyte differentiation / side of membrane / cellular response to transforming growth factor beta stimulus / positive regulation of protein metabolic process / embryo implantation / positive regulation of endothelial cell migration / extracellular matrix / extracellular matrix organization / axonogenesis / negative regulation of cell migration / cytokine activity / positive regulation of JNK cascade / intracellular protein transport / trans-Golgi network / Schaffer collateral - CA1 synapse / neuron differentiation / Wnt signaling pathway / negative regulation of neurogenesis / Golgi lumen / response to estrogen / positive regulation of canonical Wnt signaling pathway / endocytic vesicle membrane / serine-type endopeptidase inhibitor activity / response to estradiol / early endosome membrane / presynapse / positive regulation of canonical NF-kappaB signal transduction / cytoplasmic vesicle / angiogenesis / early endosome / receptor ligand activity / Golgi membrane / endoplasmic reticulum lumen / signaling receptor binding 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: 3.23 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
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_41765.map.gz | 117.9 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-41765-v30.xml emd-41765.xml | 17.7 KB 17.7 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_41765.png | 48.2 KB | ||
Filedesc metadata | emd-41765.cif.gz | 6.5 KB | ||
その他 | emd_41765_half_map_1.map.gz emd_41765_half_map_2.map.gz | 116 MB 116 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-41765 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-41765 | 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_41765.map.gz / 形式: CCP4 / 大きさ: 125 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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ボクセルのサイズ | X=Y=Z: 0.83 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
-ハーフマップ: #1
ファイル | emd_41765_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_41765_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 : Wnt7a-WLS-RECK Complex
全体 | 名称: Wnt7a-WLS-RECK Complex |
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要素 |
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-超分子 #1: Wnt7a-WLS-RECK Complex
超分子 | 名称: Wnt7a-WLS-RECK Complex / タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1-#3 |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
-分子 #1: Protein Wnt-7a
分子 | 名称: Protein Wnt-7a / 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: 39.062977 KDa |
組換発現 | 生物種: Homo sapiens (ヒト) |
配列 | 文字列: MNRKARRCLG HLFLSLGMVY LRIGGFSSVV ALGASIICNK IPGLAPRQRA ICQSRPDAII VIGEGSQMGL DECQFQFRNG RWNCSALGE RTVFGKELKV GSREAAFTYA IIAAGVAHAI TAACTQGNLS DCGCDKEKQG QYHRDEGWKW GGCSADIRYG I GFAKVFVD ...文字列: MNRKARRCLG HLFLSLGMVY LRIGGFSSVV ALGASIICNK IPGLAPRQRA ICQSRPDAII VIGEGSQMGL DECQFQFRNG RWNCSALGE RTVFGKELKV GSREAAFTYA IIAAGVAHAI TAACTQGNLS DCGCDKEKQG QYHRDEGWKW GGCSADIRYG I GFAKVFVD AREIKQNART LMNLHNNEAG RKILEENMKL ECKCHGVSGS CTTKTCWTTL PQFRELGYVL KDKYNEAVHV EP VRASRNK RPTFLKIKKP LSYRKPMDTD LVYIEKSPNY CEEDPVTGSV GTQGRACNKT APQASGCDLM CCGRGYNTHQ YAR VWQCNC KFHWCCYVKC NTCSERTEMY TCK UniProtKB: Protein Wnt-7a |
-分子 #2: Protein wntless homolog
分子 | 名称: Protein wntless homolog / 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: 62.317973 KDa |
組換発現 | 生物種: Homo sapiens (ヒト) |
配列 | 文字列: MAGAIIENMS TKKLCIVGGI LLVFQIIAFL VGGLIAPGPT TAVSYMSVKC VDARKNHHKT KWFVPWGPNH CDKIRDIEEA IPREIEAND IVFSVHIPLP HMEMSPWFQF MLFILQLDIA FKLNNQIREN AEVSMDVSLA YRDDAFAEWT EMAHERVPRK L KCTFTSPK ...文字列: MAGAIIENMS TKKLCIVGGI LLVFQIIAFL VGGLIAPGPT TAVSYMSVKC VDARKNHHKT KWFVPWGPNH CDKIRDIEEA IPREIEAND IVFSVHIPLP HMEMSPWFQF MLFILQLDIA FKLNNQIREN AEVSMDVSLA YRDDAFAEWT EMAHERVPRK L KCTFTSPK TPEHEGRYYE CDVLPFMEIG SVAHKFYLLN IRLPVNEKKK INVGIGEIKD IRLVGIHQNG GFTKVWFAMK TF LTPSIFI IMVWYWRRIT MMSRPPVLLE KVIFALGISM TFINIPVEWF SIGFDWTWML LFGDIRQGIF YAMLLSFWII FCG EHMMDQ HERNHIAGYW KQVGPIAVGS FCLFIFDMCE RGVQLTNPFY SIWTTDIGTE LAMAFIIVAG ICLCLYFLFL CFMV FQVFR NISGKQSSLP AMSKVRRLHY EGLIFRFKFL MLITLACAAM TVIFFIVSQV TEGHWKWGGV TVQVNSAFFT GIYGM WNLY VFALMFLYAP SHKNYGEDQS NGDLGVHSGE ELQLTTTITH VDGPTEIYKL TRKEAQE UniProtKB: Protein wntless homolog |
-分子 #3: Reversion-inducing cysteine-rich protein with Kazal motifs
分子 | 名称: Reversion-inducing cysteine-rich protein with Kazal motifs 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: 106.573461 KDa |
組換発現 | 生物種: Homo sapiens (ヒト) |
配列 | 文字列: MATVRASLRG ALLLLLAVAG VAEVAGGLAP GSAGALCCNH SKDNQMCRDV CEQIFSSKSE SRLKHLLQRA PDYCPETMVE IWNCMNSSL PGVFKKSDGW VGLGCCELAI ALECRQACKQ ASSKNDISKV CRKEYENALF SCISRNEMGS VCCSYAGHHT N CREYCQAI ...文字列: MATVRASLRG ALLLLLAVAG VAEVAGGLAP GSAGALCCNH SKDNQMCRDV CEQIFSSKSE SRLKHLLQRA PDYCPETMVE IWNCMNSSL PGVFKKSDGW VGLGCCELAI ALECRQACKQ ASSKNDISKV CRKEYENALF SCISRNEMGS VCCSYAGHHT N CREYCQAI FRTDSSPGPS QIKAVENYCA SISPQLIHCV NNYTQSYPMR NPTDSLYCCD RAEDHACQNA CKRILMSKKT EM EIVDGLI EGCKTQPLPQ DPLWQCFLES SQSVHPGVTV HPPPSTGLDG AKLHCCSKAN TSTCRELCTK LYSMSWGNTQ SWQ EFDRFC EYNPVEVSML TCLADVREPC QLGCRNLTYC TNFNNRPTEL FRSCNAQSDQ GAMNDMKLWE KGSIKMPFIN IPVL DIKKC QPEMWKAIAC SLQIKPCHSK SRGSIICKSD CVEILKKCGD QNKFPEDHTA ESICELLSPT DDLKNCIPLD TYLRP STLG NIVEEVTHPC NPNPCPANEL CEVNRKGCPS GDPCLPYFCV QGCKLGEASD FIVRQGTLIQ VPSSAGEVGC YKICSC GQS GLLENCMEMH CIDLQKSCIV GGKRKSHGTS FSIDCNVCSC FAGNLVCSTR LCLSEHSSED DRRTFTGLPC NCADQFV PV CGQNGRTYPS ACIARCVGLQ DHQFEFGSCM SKDPCNPNPC QKNQRCIPKP QVCLTTFDKF GCSQYECVPR QLACDQVQ D PVCDTDHMEH NNLCTLYQRG KSLSYKGPCQ PFCRATEPVC GHNGETYSSV CAAYSDRVAV DYYGDCQAVG VLSEHSSVA ECASVKCPSL LAAGCKPIIP PGACCPLCAG MLRVLFDKEK LDTIAKVTNK KPITVLEILQ KIRMHVSVPQ CDVFGYFSIE SEIVILIIP VDHYPKALQI EACNKEAEKI ESLINSDSPT LASHVPLSAL IISQVQVSSS VPSAGVRARP SCHSLLLPLS L GLALHLLW TYN UniProtKB: Reversion-inducing cysteine-rich protein with Kazal motifs |
-分子 #4: PALMITOLEIC ACID
分子 | 名称: PALMITOLEIC ACID / タイプ: ligand / ID: 4 / コピー数: 1 / 式: PAM |
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分子量 | 理論値: 254.408 Da |
Chemical component information | ChemComp-PAM: |
-分子 #5: (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(tri...
分子 | 名称: (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate タイプ: ligand / ID: 5 / コピー数: 1 / 式: POV |
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分子量 | 理論値: 760.076 Da |
Chemical component information | ChemComp-POV: |
-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: 7.5 |
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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: 60.0 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 / 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): 1.0 µm |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
-画像解析
初期モデル | モデルのタイプ: OTHER |
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最終 再構成 | 解像度のタイプ: BY AUTHOR / 解像度: 3.23 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 87543 |
初期 角度割当 | タイプ: NOT APPLICABLE |
最終 角度割当 | タイプ: NOT APPLICABLE |