+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-0358 | |||||||||
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タイトル | Cryo-EM structure of tetrameric Ptch1 in complex with ShhNp (form II) | |||||||||
マップデータ | em-volume_P1 | |||||||||
試料 |
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キーワード | Receptor / RND family / PROTEIN BINDING | |||||||||
機能・相同性 | 機能・相同性情報 morphogen activity / positive regulation of skeletal muscle cell proliferation / neural plate axis specification / right lung development / left lung development / primary prostatic bud elongation / regulation of mesenchymal cell proliferation involved in prostate gland development / mesenchymal smoothened signaling pathway involved in prostate gland development / positive regulation of sclerotome development / tracheoesophageal septum formation ...morphogen activity / positive regulation of skeletal muscle cell proliferation / neural plate axis specification / right lung development / left lung development / primary prostatic bud elongation / regulation of mesenchymal cell proliferation involved in prostate gland development / mesenchymal smoothened signaling pathway involved in prostate gland development / positive regulation of sclerotome development / tracheoesophageal septum formation / negative regulation of ureter smooth muscle cell differentiation / positive regulation of ureter smooth muscle cell differentiation / negative regulation of kidney smooth muscle cell differentiation / positive regulation of kidney smooth muscle cell differentiation / hindgut morphogenesis / regulation of odontogenesis / cell differentiation involved in kidney development / positive regulation of mesenchymal cell proliferation involved in ureter development / hedgehog receptor activity / response to chlorate / neural tube patterning / trunk neural crest cell migration / Formation of lateral plate mesoderm / cell proliferation involved in metanephros development / polarity specification of anterior/posterior axis / striated muscle tissue development / negative regulation of alpha-beta T cell differentiation / regulation of glial cell proliferation / regulation of prostatic bud formation / ventral midline development / metanephric mesenchymal cell proliferation involved in metanephros development / smoothened binding / formation of anatomical boundary / lung epithelium development / cholesterol-protein transferase activity / positive regulation of striated muscle cell differentiation / hedgehog family protein binding / trachea morphogenesis / bud outgrowth involved in lung branching / HHAT G278V doesn't palmitoylate Hh-Np / telencephalon regionalization / epithelial-mesenchymal cell signaling / Ligand-receptor interactions / laminin-1 binding / limb bud formation / hindlimb morphogenesis / lung lobe morphogenesis / negative regulation of cholesterol efflux / limb morphogenesis / salivary gland cavitation / spinal cord dorsal/ventral patterning / negative regulation of mesenchymal cell apoptotic process / embryonic digestive tract morphogenesis / determination of left/right asymmetry in lateral mesoderm / epithelial cell proliferation involved in salivary gland morphogenesis / positive regulation of cerebellar granule cell precursor proliferation / negative regulation of T cell differentiation in thymus / epidermal cell fate specification / spinal cord motor neuron differentiation / cell development / positive regulation of T cell differentiation in thymus / Activation of SMO / mesenchymal cell proliferation involved in lung development / cerebellar granule cell precursor proliferation / intermediate filament organization / prostate gland development / lymphoid progenitor cell differentiation / embryonic skeletal system development / establishment of epithelial cell polarity / skeletal muscle fiber differentiation / somite development / mesenchymal cell apoptotic process / patched binding / negative regulation of cell division / neuron fate commitment / animal organ formation / embryonic foregut morphogenesis / hindbrain development / ectoderm development / positive regulation of skeletal muscle tissue development / stem cell development / embryonic pattern specification / branching involved in salivary gland morphogenesis / thalamus development / negative regulation of dopaminergic neuron differentiation / skeletal muscle cell proliferation / CD4-positive or CD8-positive, alpha-beta T cell lineage commitment / cellular response to cholesterol / positive regulation of immature T cell proliferation in thymus / dorsal/ventral neural tube patterning / negative thymic T cell selection / smooth muscle tissue development / self proteolysis / pattern specification process / male genitalia development / artery development / lung-associated mesenchyme development / positive regulation of astrocyte differentiation / oligodendrocyte development / pharyngeal system development 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: 6.5 Å | |||||||||
データ登録者 | Yan N / Gong X | |||||||||
資金援助 | 米国, 1件
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引用 | ジャーナル: Nat Commun / 年: 2019 タイトル: Inhibition of tetrameric Patched1 by Sonic Hedgehog through an asymmetric paradigm. 著者: Hongwu Qian / Pingping Cao / Miaohui Hu / Shuai Gao / Nieng Yan / Xin Gong / 要旨: The Hedgehog (Hh) pathway controls embryonic development and postnatal tissue maintenance and regeneration. Inhibition of Hh receptor Patched (Ptch) by the Hh ligands relieves suppression of ...The Hedgehog (Hh) pathway controls embryonic development and postnatal tissue maintenance and regeneration. Inhibition of Hh receptor Patched (Ptch) by the Hh ligands relieves suppression of signaling cascades. Here, we report the cryo-EM structure of tetrameric Ptch1 in complex with the palmitoylated N-terminal signaling domain of human Sonic hedgehog (ShhN) at a 4:2 stoichiometric ratio. The structure shows that four Ptch1 protomers are organized as a loose dimer of dimers. Each dimer binds to one ShhN through two distinct inhibitory interfaces, one mainly through the N-terminal peptide and the palmitoyl moiety of ShhN and the other through the Ca-mediated interface on ShhN. Map comparison reveals that the cholesteryl moiety of native ShhN occupies a recently identified extracellular steroid binding pocket in Ptch1. Our structure elucidates the tetrameric assembly of Ptch1 and suggests an asymmetric mode of action of the Hh ligands for inhibiting the potential cholesterol transport activity of Ptch1. | |||||||||
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_0358.map.gz | 77.1 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-0358-v30.xml emd-0358.xml | 15.5 KB 15.5 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_0358.png | 67.5 KB | ||
Filedesc metadata | emd-0358.cif.gz | 6.7 KB | ||
その他 | emd_0358_additional.map.gz | 6.1 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-0358 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-0358 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_0358_validation.pdf.gz | 503.7 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_0358_full_validation.pdf.gz | 503.3 KB | 表示 | |
XML形式データ | emd_0358_validation.xml.gz | 6.2 KB | 表示 | |
CIF形式データ | emd_0358_validation.cif.gz | 7.2 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-0358 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-0358 | HTTPS FTP |
-関連構造データ
関連構造データ | 6n7kMC 0355C 0356C 6n7gC 6n7hC M: このマップから作成された原子モデル C: 同じ文献を引用 (文献) |
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類似構造データ | |
電子顕微鏡画像生データ | EMPIAR-10456 (タイトル: Tetrameric Ptch1 complexed with ShhNp / Data size: 8.9 TB Data #1: Oligomeric complex of Ptch1 and Shhp [micrographs - multiframe]) |
-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_0358.map.gz / 形式: CCP4 / 大きさ: 83.7 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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注釈 | em-volume_P1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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: 1.114 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: em-additional-volume P1
ファイル | emd_0358_additional.map | ||||||||||||
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注釈 | em-additional-volume_P1 | ||||||||||||
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 : Patch1
全体 | 名称: Patch1 |
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要素 |
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-超分子 #1: Patch1
超分子 | 名称: Patch1 / タイプ: organelle_or_cellular_component / ID: 1 / 親要素: 0 / 含まれる分子: #1 |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
-分子 #1: Protein patched homolog 1
分子 | 名称: Protein patched homolog 1 / タイプ: protein_or_peptide / ID: 1 / コピー数: 4 / 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: 150.189578 KDa |
組換発現 | 生物種: Homo sapiens (ヒト) |
配列 | 文字列: MADYKDDDDK SGPDEVDASG RMASAGNAAE PQDRGGGGSG CIGAPGRPAG GGRRRRTGGL RRAAAPDRDY LHRPSYCDAA FALEQISKG KATGRKAPLW LRAKFQRLLF KLGCYIQKNC GKFLVVGLLI FGAFAVGLKA ANLETNVEEL WVEVGGRVSR E LNYTRQKI ...文字列: MADYKDDDDK SGPDEVDASG RMASAGNAAE PQDRGGGGSG CIGAPGRPAG GGRRRRTGGL RRAAAPDRDY LHRPSYCDAA FALEQISKG KATGRKAPLW LRAKFQRLLF KLGCYIQKNC GKFLVVGLLI FGAFAVGLKA ANLETNVEEL WVEVGGRVSR E LNYTRQKI GEEAMFNPQL MIQTPKEEGA NVLTTEALLQ HLDSALQASR VHVYMYNRQW KLEHLCYKSG ELITETGYMD QI IEYLYPC LIITPLDCFW EGAKLQSGTA YLLGKPPLRW TNFDPLEFLE ELKKINYQVD SWEEMLNKAE VGHGYMDRPC LNP ADPDCP ATAPNKNSTK PLDMALVLNG GCHGLSRKYM HWQEELIVGG TVKNSTGKLV SAHALQTMFQ LMTPKQMYEH FKGY EYVSH INWNEDKAAA ILEAWQRTYV EVVHQSVAQN STQKVLSFTT TTLDDILKSF SDVSVIRVAS GYLLMLAYAC LTMLR WDCS KSQGAVGLAG VLLVALSVAA GLGLCSLIGI SFNAATTQVL PFLALGVGVD DVFLLAHAFS ETGQNKRIPF EDRTGE CLK RTGASVALTS ISNVTAFFMA ALIPIPALRA FSLQAAVVVV FNFAMVLLIF PAILSMDLYR REDRRLDIFC CFTSPCV SR VIQVEPQAYT DTHDNTRYSP PPPYSSHSFA HETQITMQST VQLRTEYDPH THVYYTTAEP RSEISVQPVT VTQDTLSC Q SPESTSSTRD LLSQFSDSSL HCLEPPCTKW TLSSFAEKHY APFLLKPKAK VVVIFLFLGL LGVSLYGTTR VRDGLDLTD IVPRETREYD FIAAQFKYFS FYNMYIVTQK ADYPNIQHLL YDLHRSFSNV KYVMLEENKQ LPKMWLHYFR DWLQGLQDAF DSDWETGKI MPNNYKNGSD DGVLAYKLLV QTGSRDKPID ISQLTKQRLV DADGIINPSA FYIYLTAWVS NDPVAYAASQ A NIRPHRPE WVHDKADYMP ETRLRIPAAE PIEYAQFPFY LNGLRDTSDF VEAIEKVRTI CSNYTSLGLS SYPNGYPFLF WE QYIGLRH WLLLFISVVL ACTFLVCAVF LLNPWTAGII VMVLALMTVE LFGMMGLIGI KLSAVPVVIL IASVGIGVEF TVH VALAFL TAIGDKNRRA VLALEHMFAP VLDGAVSTLL GVLMLAGSEF DFIVRYFFAV LAILTILGVL NGLVLLPVLL SFFG PYPEV SPANGLNRLP TPSPEPPPSV VRFAMPPGHT HSGSDSSDSE YSSQTTVSGL SEELRHYEAQ QGAGGPAHQV IVEAT ENPV FAHSTVVHPE SRHHPPSNPR QQPHLDSGSL PPGRQGQQPR RDLEGSDEVD AVEGSHHHHH HHHHH UniProtKB: Protein patched homolog 1 |
-分子 #2: Sonic hedgehog protein
分子 | 名称: Sonic hedgehog protein / タイプ: protein_or_peptide / ID: 2 / コピー数: 2 / 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: 19.594039 KDa |
組換発現 | 生物種: Homo sapiens (ヒト) |
配列 | 文字列: CGPGRGFGKR RHPKKLTPLA YKQFIPNVAE KTLGASGRYE GKISRNSERF KELTPNYNPD IIFKDEENTG ADRLMTQRCK DKLNALAIS VMNQWPGVKL RVTEGWDEDG HHSEESLHYE GRAVDITTSD RDRSKYGMLA RLAVEAGFDW VYYESKAHIH C SVKAENSV AAKSGG UniProtKB: Sonic hedgehog protein |
-分子 #4: 2-acetamido-2-deoxy-beta-D-glucopyranose
分子 | 名称: 2-acetamido-2-deoxy-beta-D-glucopyranose / タイプ: ligand / ID: 4 / コピー数: 20 / 式: NAG |
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分子量 | 理論値: 221.208 Da |
Chemical component information | ChemComp-NAG: |
-分子 #5: CHOLESTEROL
分子 | 名称: CHOLESTEROL / タイプ: ligand / ID: 5 / コピー数: 10 / 式: CLR |
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分子量 | 理論値: 386.654 Da |
Chemical component information | ChemComp-CLR: |
-分子 #6: ZINC ION
分子 | 名称: ZINC ION / タイプ: ligand / ID: 6 / コピー数: 2 / 式: ZN |
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分子量 | 理論値: 65.409 Da |
-分子 #7: CALCIUM ION
分子 | 名称: CALCIUM ION / タイプ: ligand / ID: 7 / コピー数: 4 / 式: CA |
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分子量 | 理論値: 40.078 Da |
-分子 #8: PALMITIC ACID
分子 | 名称: PALMITIC ACID / タイプ: ligand / ID: 8 / コピー数: 2 / 式: PLM |
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分子量 | 理論値: 256.424 Da |
Chemical component information | ChemComp-PLM: |
-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
濃度 | 15 mg/mL |
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緩衝液 | pH: 8 |
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 K2 SUMMIT (4k x 4k) 検出モード: SUPER-RESOLUTION / 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 |
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: RANDOM CONICAL TILT |
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最終 再構成 | 解像度のタイプ: BY AUTHOR / 解像度: 6.5 Å / 解像度の算出法: FSC 0.143 CUT-OFF / ソフトウェア - 名称: RELION / 使用した粒子像数: 25510 |
初期 角度割当 | タイプ: PROJECTION MATCHING / ソフトウェア - 名称: RELION |
最終 角度割当 | タイプ: MAXIMUM LIKELIHOOD / ソフトウェア - 名称: RELION |