登録情報 データベース : EMDB / ID : EMD-0355 構造の表示 ダウンロードとリンクタイトル Cryo-EM structure of tetrameric Ptch1 in complex with ShhNp (form I) マップデータem-volume_P1 詳細 試料細胞器官・細胞要素 : Patch1タンパク質・ペプチド : Protein patched homolog 1タンパク質・ペプチド : Sonic hedgehog proteinリガンド : 2-acetamido-2-deoxy-beta-D-glucopyranoseリガンド : CHOLESTEROLリガンド : ZINC IONリガンド : CALCIUM IONリガンド : PALMITIC ACID 残り3件を表示 表示を減らす 詳細機能・相同性 機能・相同性情報分子機能 ドメイン・相同性 構成要素
Formation of lateral plate mesoderm / 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 ... Formation of lateral plate mesoderm / 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 / polarity specification of anterior/posterior axis / trunk neural crest cell migration / hedgehog receptor activity / response to chlorate / neural tube patterning / cell proliferation involved in metanephros development / hindgut morphogenesis / 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 / laminin-1 binding / Ligand-receptor interactions / hindlimb morphogenesis / salivary gland cavitation / negative regulation of cholesterol efflux / determination of left/right asymmetry in lateral mesoderm / spinal cord dorsal/ventral patterning / negative regulation of mesenchymal cell apoptotic process / cell development / 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 / positive regulation of T cell differentiation in thymus / intermediate filament organization / cerebellar granule cell precursor proliferation / mesenchymal cell apoptotic process / embryonic skeletal system development / limb bud formation / lung lobe morphogenesis / prostate gland development / Activation of SMO / skeletal muscle fiber differentiation / establishment of epithelial cell polarity / limb morphogenesis / thalamus development / embryonic digestive tract morphogenesis / embryonic foregut morphogenesis / somite development / patched binding / negative regulation of cell division / epithelial cell proliferation involved in salivary gland morphogenesis / hindbrain development / positive regulation of skeletal muscle tissue development / animal organ formation / ectoderm development / neuron fate commitment / stem cell development / cellular response to cholesterol / dorsal/ventral neural tube patterning / negative regulation of dopaminergic neuron differentiation / mesenchymal cell proliferation involved in lung development / negative thymic T cell selection / skeletal muscle cell proliferation / lymphoid progenitor cell differentiation / positive regulation of immature T cell proliferation in thymus / CD4-positive or CD8-positive, alpha-beta T cell lineage commitment / smooth muscle tissue development / regulation of stem cell proliferation / oligodendrocyte development / male genitalia development / artery development / positive regulation of astrocyte differentiation / pattern specification process / self proteolysis / pharyngeal system development / epithelial cell proliferation involved in prostate gland development / mammary gland epithelial cell differentiation 類似検索 - 分子機能 Transmembrane receptor, patched / Hedgehog, N-terminal signalling domain / Hedgehog protein / Hedgehog protein, Hint domain / Hint module / Hedgehog amino-terminal signalling domain / Hedgehog signalling/DD-peptidase zinc-binding domain superfamily / Protein patched/dispatched / Patched family / Sterol-sensing domain (SSD) profile. ... Transmembrane receptor, patched / Hedgehog, N-terminal signalling domain / Hedgehog protein / Hedgehog protein, Hint domain / Hint module / Hedgehog amino-terminal signalling domain / Hedgehog signalling/DD-peptidase zinc-binding domain superfamily / Protein patched/dispatched / Patched family / Sterol-sensing domain (SSD) profile. / Sterol-sensing domain / Hint domain C-terminal / Hint (Hedgehog/Intein) domain C-terminal region / Intein N-terminal splicing region / Intein N-terminal splicing motif profile. / Hint domain N-terminal / Hint (Hedgehog/Intein) domain N-terminal region / Hint domain superfamily 類似検索 - ドメイン・相同性 Protein patched homolog 1 / Sonic hedgehog protein 類似検索 - 構成要素生物種 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 : 6.8 Å 詳細 データ登録者Yan N / Gong X / Qian HW 資金援助 米国, 1件 詳細 詳細を隠すOrganization Grant number 国 National Science Foundation (NSF, United States) DMR-1420541 米国
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 登録 2018年11月27日 - ヘッダ(付随情報) 公開 2019年5月29日 - マップ公開 2019年5月29日 - 更新 2020年7月29日 - 現状 2020年7月29日 処理サイト : RCSB / 状態 : 公開
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