+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-7796 | |||||||||
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タイトル | Structure of human Patched1 in complex with native Sonic Hedgehog | |||||||||
マップデータ | A protein structure | |||||||||
試料 |
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機能・相同性 | 機能・相同性情報 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 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 / morphogen activity / 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 / hindgut morphogenesis / 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 / metanephric mesenchymal cell proliferation involved in metanephros development / smoothened binding / formation of anatomical boundary / lung epithelium development / positive regulation of striated muscle cell differentiation / ventral midline development / hedgehog family protein binding / trachea morphogenesis / cholesterol-protein transferase activity / 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 / hindlimb morphogenesis / limb bud formation / 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 / determination of left/right asymmetry in lateral mesoderm / embryonic digestive tract morphogenesis / positive regulation of cerebellar granule cell precursor proliferation / negative regulation of T cell differentiation in thymus / epithelial cell proliferation involved in salivary gland morphogenesis / epidermal cell fate specification / spinal cord motor neuron differentiation / cell development / positive regulation of T cell differentiation in thymus / mesenchymal cell proliferation involved in lung development / intermediate filament organization / prostate gland development / cerebellar granule cell precursor proliferation / Activation of SMO / embryonic skeletal system development / establishment of epithelial cell polarity / skeletal muscle fiber differentiation / mesenchymal cell apoptotic process / patched binding / negative regulation of cell division / somite development / animal organ formation / embryonic foregut morphogenesis / hindbrain development / neuron fate commitment / ectoderm development / positive regulation of skeletal muscle tissue development / stem cell development / thalamus development / negative regulation of dopaminergic neuron differentiation / embryonic pattern specification / branching involved in salivary gland morphogenesis / skeletal muscle cell proliferation / lymphoid progenitor cell differentiation / positive regulation of immature T cell proliferation in thymus / cellular response to cholesterol / dorsal/ventral neural tube patterning / negative thymic T cell selection / CD4-positive or CD8-positive, alpha-beta T cell lineage commitment / smooth muscle tissue development / pattern specification process / artery development / lung-associated mesenchyme development / positive regulation of astrocyte differentiation / oligodendrocyte development / pharyngeal system development / male genitalia development / regulation of stem cell proliferation 類似検索 - 分子機能 | |||||||||
生物種 | Homo sapiens (ヒト) | |||||||||
手法 | 単粒子再構成法 / 解像度: 3.5 Å | |||||||||
データ登録者 | Qi X / Li X | |||||||||
引用 | ジャーナル: Nature / 年: 2018 タイトル: Structures of human Patched and its complex with native palmitoylated sonic hedgehog. 著者: Xiaofeng Qi / Philip Schmiege / Elias Coutavas / Jiawei Wang / Xiaochun Li / 要旨: Hedgehog (HH) signalling governs embryogenesis and adult tissue homeostasis in mammals and other multicellular organisms. Whereas deficient HH signalling leads to birth defects, unrestrained HH ...Hedgehog (HH) signalling governs embryogenesis and adult tissue homeostasis in mammals and other multicellular organisms. Whereas deficient HH signalling leads to birth defects, unrestrained HH signalling is implicated in human cancers. N-terminally palmitoylated HH releases the repression of Patched to the oncoprotein smoothened (SMO); however, the mechanism by which HH recognizes Patched is unclear. Here we report cryo-electron microscopy structures of human patched 1 (PTCH1) alone and in complex with the N-terminal domain of 'native' sonic hedgehog (native SHH-N has both a C-terminal cholesterol and an N-terminal fatty-acid modification), at resolutions of 3.5 Å and 3.8 Å, respectively. The structure of PTCH1 has internal two-fold pseudosymmetry in the transmembrane core, which features a sterol-sensing domain and two homologous extracellular domains, resembling the architecture of Niemann-Pick C1 (NPC1) protein. The palmitoylated N terminus of SHH-N inserts into a cavity between the extracellular domains of PTCH1 and dominates the PTCH1-SHH-N interface, which is distinct from that reported for SHH-N co-receptors. Our biochemical assays show that SHH-N may use another interface, one that is required for its co-receptor binding, to recruit PTCH1 in the absence of a covalently attached palmitate. Our work provides atomic insights into the recognition of the N-terminal domain of HH (HH-N) by PTCH1, offers a structural basis for cooperative binding of HH-N to various receptors and serves as a molecular framework for HH signalling and its malfunction in disease. | |||||||||
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_7796.map.gz | 59.5 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-7796-v30.xml emd-7796.xml | 12.5 KB 12.5 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_7796.png | 32.7 KB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-7796 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-7796 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_7796_validation.pdf.gz | 444.8 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_7796_full_validation.pdf.gz | 444.4 KB | 表示 | |
XML形式データ | emd_7796_validation.xml.gz | 5.4 KB | 表示 | |
CIF形式データ | emd_7796_validation.cif.gz | 6.2 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-7796 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-7796 | 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_7796.map.gz / 形式: CCP4 / 大きさ: 64 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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注釈 | A protein structure | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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 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
-試料の構成要素
-全体 : Ptc
全体 | 名称: Ptc |
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要素 |
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-超分子 #1: Ptc
超分子 | 名称: Ptc / タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1-#2 |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
組換発現 | 生物種: Homo sapiens (ヒト) |
分子量 | 実験値: 121 KDa |
-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: 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: 160.714406 KDa |
組換発現 | 生物種: Homo sapiens (ヒト) |
配列 | 文字列: MASAGNAAEP QDRGGGGSGC IGAPGRPAGG GRRRRTGGLR RAAAPDRDYL HRPSYCDAAF ALEQISKGKA TGRKAPLWLR AKFQRLLFK LGCYIQKNCG KFLVVGLLIF GAFAVGLKAA NLETNVEELW VEVGGRVSRE LNYTRQKIGE EAMFNPQLMI Q TPKEEGAN ...文字列: MASAGNAAEP QDRGGGGSGC IGAPGRPAGG GRRRRTGGLR RAAAPDRDYL HRPSYCDAAF ALEQISKGKA TGRKAPLWLR AKFQRLLFK LGCYIQKNCG KFLVVGLLIF GAFAVGLKAA NLETNVEELW VEVGGRVSRE LNYTRQKIGE EAMFNPQLMI Q TPKEEGAN VLTTEALLQH LDSALQASRV HVYMYNRQWK LEHLCYKSGE LITETGYMDQ IIEYLYPCLI ITPLDCFWEG AK LQSGTAY LLGKPPLRWT NFDPLEFLEE LKKINYQVDS WEEMLNKAEV GHGYMDRPCL NPADPDCPAT APNKNSTKPL DMA LVLNGG CHGLSRKYMH WQEELIVGGT VKNSTGKLVS AHALQTMFQL MTPKQMYEHF KGYEYVSHIN WNEDKAAAIL EAWQ RTYVE VVHQSVAQNS TQKVLSFTTT TLDDILKSFS DVSVIRVASG YLLMLAYACL TMLRWDCSKS QGAVGLAGVL LVALS VAAG LGLCSLIGIS FNAATTQVLP FLALGVGVDD VFLLAHAFSE TGQNKRIPFE DRTGECLKRT GASVALTSIS NVTAFF MAA LIPIPALRAF SLQAAVVVVF NFAMVLLIFP AILSMDLYRR EDRRLDIFCC FTSPCVSRVI QVEPQAYTDT HDNTRYS PP PPYSSHSFAH ETQITMQSTV QLRTEYDPHT HVYYTTAEPR SEISVQPVTV TQDTLSCQSP ESTSSTRDLL SQFSDSSL H CLEPPCTKWT LSSFAEKHYA PFLLKPKAKV VVIFLFLGLL GVSLYGTTRV RDGLDLTDIV PRETREYDFI AAQFKYFSF YNMYIVTQKA DYPNIQHLLY DLHRSFSNVK YVMLEENKQL PKMWLHYFRD WLQGLQDAFD SDWETGKIMP NNYKNGSDDG VLAYKLLVQ TGSRDKPIDI SQLTKQRLVD ADGIINPSAF YIYLTAWVSN DPVAYAASQA NIRPHRPEWV HDKADYMPET R LRIPAAEP IEYAQFPFYL NGLRDTSDFV EAIEKVRTIC SNYTSLGLSS YPNGYPFLFW EQYIGLRHWL LLFISVVLAC TF LVCAVFL LNPWTAGIIV MVLALMTVEL FGMMGLIGIK LSAVPVVILI ASVGIGVEFT VHVALAFLTA IGDKNRRAVL ALE HMFAPV LDGAVSTLLG VLMLAGSEFD FIVRYFFAVL AILTILGVLN GLVLLPVLLS FFGPYPEVSP ANGLNRLPTP SPEP PPSVV RFAMPPGHTH SGSDSSDSEY SSQTTVSGLS EELRHYEAQQ GAGGPAHQVI VEATENPVFA HSTVVHPESR HHPPS NPRQ QPHLDSGSLP PGRQGQQPRR DPPREGLWPP PYRPRRDAFE ISTEGHSGPS NRARWGPRGA RSHNPRNPAS TAMGSS VPG YCQPITTVTA SASVTVAVHP PPVPGPGRNP RGGLCPGYPE TDHGLFEDPH VPFHVRCERR DSKVEVIELQ DVECEER PR GSSSN |
-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: 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: 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 |
-分子 #3: N-ACETYL-D-GLUCOSAMINE
分子 | 名称: N-ACETYL-D-GLUCOSAMINE / タイプ: ligand / ID: 3 / コピー数: 6 / 式: NAG |
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分子量 | 理論値: 221.208 Da |
-分子 #4: ZINC ION
分子 | 名称: ZINC ION / タイプ: ligand / ID: 4 / コピー数: 1 / 式: ZN |
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分子量 | 理論値: 65.409 Da |
-分子 #5: PALMITIC ACID
分子 | 名称: PALMITIC ACID / タイプ: ligand / ID: 5 / コピー数: 1 / 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
解析 | 単粒子再構成法 |
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試料の集合状態 | particle |
-試料調製
緩衝液 | pH: 7 |
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-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) 平均電子線量: 1.6 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: DARK 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: PDB ENTRY PDBモデル - PDB ID: |
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最終 再構成 | 解像度のタイプ: BY AUTHOR / 解像度: 3.5 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 789118 |
初期 角度割当 | タイプ: ANGULAR RECONSTITUTION |
最終 角度割当 | タイプ: ANGULAR RECONSTITUTION |