登録情報 データベース : EMDB / ID : EMD-30958 構造の表示 ダウンロードとリンクタイトル Cryo-EM structure of hDisp1NNN-ShhN マップデータ 詳細 試料複合体 : hDisp1NNN-ShhN複合体 : ShhNタンパク質・ペプチド : Sonic hedgehog protein複合体 : hDisp1NNNタンパク質・ペプチド : Protein dispatched homolog 1リガンド : ZINC IONリガンド : CHOLESTEROL HEMISUCCINATEリガンド : 2-acetamido-2-deoxy-beta-D-glucopyranose 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
patched ligand maturation / morphogen activity / 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 ... patched ligand maturation / morphogen activity / 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 / hindgut morphogenesis / regulation of odontogenesis / positive regulation of mesenchymal cell proliferation involved in ureter development / trunk neural crest cell migration / Formation of lateral plate mesoderm / 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 / formation of anatomical boundary / lung epithelium development / cholesterol-protein transferase activity / positive regulation of striated muscle cell differentiation / trachea morphogenesis / bud outgrowth involved in lung branching / HHAT G278V doesn't palmitoylate Hh-Np / diaphragm development / telencephalon regionalization / epithelial-mesenchymal cell signaling / Ligand-receptor interactions / laminin-1 binding / limb bud formation / lung lobe morphogenesis / negative regulation of cholesterol efflux / 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 / 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 / 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 / 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 / regulation of stem cell proliferation / epithelial cell proliferation involved in prostate gland development / positive regulation of epithelial cell proliferation involved in prostate gland development / Release of Hh-Np from the secreting cell / dopaminergic neuron differentiation / intein-mediated protein splicing / glycosaminoglycan binding / regulation of proteolysis / Formation of axial mesoderm / metanephric collecting duct development / metanephros development / positive thymic T cell selection 類似検索 - 分子機能 : / 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 ... : / 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 Sonic hedgehog protein / Protein dispatched homolog 1 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 : 4.07 Å 詳細 データ登録者Li W / Wang L / Gong X 資金援助 中国, 2件 詳細 詳細を隠すOrganization Grant number 国 Other government 中国 Other government 中国
引用ジャーナル : Nat Commun / 年 : 2021タイトル : Structural insights into proteolytic activation of the human Dispatched1 transporter for Hedgehog morphogen release.著者 : Wanqiu Li / Linlin Wang / Bradley M Wierbowski / Mo Lu / Feitong Dong / Wenchen Liu / Sisi Li / Peiyi Wang / Adrian Salic / Xin Gong / 要旨 : The membrane protein Dispatched (Disp), which belongs to the RND family of small molecule transporters, is essential for Hedgehog (Hh) signaling, by catalyzing the extracellular release of palmitate- ... The membrane protein Dispatched (Disp), which belongs to the RND family of small molecule transporters, is essential for Hedgehog (Hh) signaling, by catalyzing the extracellular release of palmitate- and cholesterol-modified Hh ligands from producing cells. Disp function requires Furin-mediated proteolytic cleavage of its extracellular domain, but how this activates Disp remains obscure. Here, we employ cryo-electron microscopy to determine atomic structures of human Disp1 (hDisp1), before and after cleavage, and in complex with lipid-modified Sonic hedgehog (Shh) ligand. These structures, together with biochemical data, reveal that proteolytic cleavage opens the extracellular domain of hDisp1, removing steric hindrance to Shh binding. Structure-guided functional experiments demonstrate the role of hDisp1-Shh interactions in ligand release. Our results clarify the mechanisms of hDisp1 activation and Shh morphogen release, and highlight how a unique proteolytic cleavage event enabled acquisition of a protein substrate by a member of a family of small molecule transporters. 履歴 登録 2021年2月5日 - ヘッダ(付随情報) 公開 2021年12月8日 - マップ公開 2021年12月8日 - 更新 2021年12月8日 - 現状 2021年12月8日 処理サイト : PDBj / 状態 : 公開
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