登録情報 データベース : EMDB / ID : EMD-7796 構造の表示 ダウンロードとリンクタイトル Structure of human Patched1 in complex with native Sonic Hedgehog マップデータA protein structure 詳細 試料複合体 : Ptc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 : N-ACETYL-D-GLUCOSAMINEリガンド : ZINC IONリガンド : PALMITIC ACID 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
regulation of nodal signaling pathway / neural plate axis specification / cell differentiation involved in kidney development / positive regulation of skeletal muscle cell proliferation / 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 ... regulation of nodal signaling pathway / neural plate axis specification / cell differentiation involved in kidney development / positive regulation of skeletal muscle cell proliferation / 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 / positive regulation of mesenchymal cell proliferation involved in ureter development / hedgehog receptor activity / response to chlorate / neural tube patterning / cell proliferation involved in metanephros development / trunk neural crest cell migration / Formation of lateral plate mesoderm / hindgut morphogenesis / polarity specification of anterior/posterior axis / regulation of glial cell proliferation / negative regulation of alpha-beta T cell differentiation / regulation of prostatic bud formation / formation of anatomical boundary / smoothened binding / positive regulation of striated muscle cell differentiation / metanephric mesenchymal cell proliferation involved in metanephros development / ventral midline development / trachea morphogenesis / hedgehog family protein binding / cholesterol-protein transferase activity / HHAT G278V doesn't palmitoylate Hh-Np / telencephalon regionalization / bud outgrowth involved in lung branching / epithelial-mesenchymal cell signaling / hindlimb morphogenesis / Ligand-receptor interactions / laminin-1 binding / lung epithelium development / negative regulation of cholesterol efflux / salivary gland cavitation / spinal cord dorsal/ventral patterning / determination of left/right asymmetry in lateral mesoderm / negative regulation of mesenchymal cell apoptotic process / positive regulation of cerebellar granule cell precursor proliferation / negative regulation of T cell differentiation in thymus / epidermal cell fate specification / cell development / spinal cord motor neuron differentiation / positive regulation of T cell differentiation in thymus / establishment of epithelial cell polarity / intermediate filament organization / prostate gland development / cerebellar granule cell precursor proliferation / limb bud formation / embryonic skeletal system development / skeletal muscle fiber differentiation / lung lobe morphogenesis / limb morphogenesis / Activation of SMO / mesenchymal cell apoptotic process / negative regulation of cell division / patched binding / animal organ formation / embryonic digestive tract morphogenesis / embryonic foregut morphogenesis / hindbrain development / positive regulation of skeletal muscle tissue development / epithelial cell proliferation involved in salivary gland morphogenesis / somite development / ectoderm development / neuron fate commitment / negative regulation of dopaminergic neuron differentiation / mesenchymal cell proliferation involved in lung development / skeletal muscle cell proliferation / stem cell development / positive regulation of immature T cell proliferation in thymus / lymphoid progenitor cell differentiation / dorsal/ventral neural tube patterning / self proteolysis / smooth muscle tissue development / artery development / cellular response to cholesterol / thalamus development / positive regulation of astrocyte differentiation / CD4-positive or CD8-positive, alpha-beta T cell lineage commitment / negative thymic T cell selection / pharyngeal system development / pattern specification process / regulation of stem cell proliferation / mammary gland duct morphogenesis / mammary gland epithelial cell differentiation / oligodendrocyte development / positive regulation of epithelial cell proliferation involved in prostate gland development 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 / : / Sterol-sensing domain of SREBP cleavage-activation ... 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 / : / Sterol-sensing domain of SREBP cleavage-activation / Sterol-sensing domain (SSD) profile. / Hint domain C-terminal / Hint (Hedgehog/Intein) domain C-terminal region / Sterol-sensing domain / 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 / 解像度 : 3.5 Å 詳細 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 登録 2018年4月18日 - ヘッダ(付随情報) 公開 2018年7月4日 - マップ公開 2018年7月11日 - 更新 2019年4月17日 - 現状 2019年4月17日 処理サイト : RCSB / 状態 : 公開
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