+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 6dmo | |||||||||
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タイトル | Cryo-EM structure of human Ptch1 with three mutations L282Q/T500F/P504L | |||||||||
要素 | Protein patched homolog 1 | |||||||||
キーワード | PROTEIN BINDING (タンパク質) / Receptor / RND family | |||||||||
機能・相同性 | 機能・相同性情報 neural plate axis specification / cell differentiation involved in kidney development / hedgehog receptor activity / response to chlorate / cell proliferation involved in metanephros development / smoothened binding / neural tube patterning / hedgehog family protein binding / Ligand-receptor interactions / hindlimb morphogenesis ...neural plate axis specification / cell differentiation involved in kidney development / hedgehog receptor activity / response to chlorate / cell proliferation involved in metanephros development / smoothened binding / neural tube patterning / hedgehog family protein binding / Ligand-receptor interactions / hindlimb morphogenesis / epidermal cell fate specification / spinal cord motor neuron differentiation / prostate gland development / Activation of SMO / negative regulation of cell division / patched binding / limb morphogenesis / somite development / dorsal/ventral neural tube patterning / cellular response to cholesterol / smooth muscle tissue development / pharyngeal system development / mammary gland duct morphogenesis / mammary gland epithelial cell differentiation / 拘束 (生物学) / commissural neuron axon guidance / metanephric collecting duct development / regulation of smoothened signaling pathway / dorsal/ventral pattern formation / Class B/2 (Secretin family receptors) / embryonic limb morphogenesis / cholesterol binding / ciliary membrane / smoothened signaling pathway / negative regulation of multicellular organism growth / branching involved in ureteric bud morphogenesis / positive regulation of epidermal cell differentiation / spermatid development / dendritic growth cone / positive regulation of cholesterol efflux / keratinocyte proliferation / negative regulation of keratinocyte proliferation / negative regulation of osteoblast differentiation / embryonic organ development / Hedgehog 'off' state / negative regulation of smoothened signaling pathway / axonal growth cone / response to mechanical stimulus / heart morphogenesis / response to retinoic acid / negative regulation of stem cell proliferation / regulation of mitotic cell cycle / cyclin binding / stem cell proliferation / neural tube closure / liver regeneration / カベオラ / protein localization to plasma membrane / animal organ morphogenesis / Hedgehog 'on' state / brain development / negative regulation of DNA-binding transcription factor activity / protein processing / endocytic vesicle membrane / regulation of protein localization / glucose homeostasis / response to estradiol / apical part of cell / heparin binding / midbody / in utero embryonic development / response to xenobiotic stimulus / intracellular membrane-bounded organelle / protein-containing complex binding / perinuclear region of cytoplasm / positive regulation of DNA-templated transcription / negative regulation of transcription by RNA polymerase II / 細胞膜 類似検索 - 分子機能 | |||||||||
生物種 | Homo sapiens (ヒト) | |||||||||
手法 | 電子顕微鏡法 / 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 4.1 Å | |||||||||
データ登録者 | Yan, N. / Gong, X. / Qian, H.W. | |||||||||
資金援助 | 中国, 2件
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引用 | ジャーナル: Science / 年: 2018 タイトル: Structural basis for the recognition of Sonic Hedgehog by human Patched1. 著者: Xin Gong / Hongwu Qian / Pingping Cao / Xin Zhao / Qiang Zhou / Jianlin Lei / Nieng Yan / 要旨: The Hedgehog (Hh) pathway involved in development and regeneration is activated by the extracellular binding of Hh to the membrane receptor Patched (Ptch). We report the structures of human Ptch1 ...The Hedgehog (Hh) pathway involved in development and regeneration is activated by the extracellular binding of Hh to the membrane receptor Patched (Ptch). We report the structures of human Ptch1 alone and in complex with the N-terminal domain of human Sonic hedgehog (ShhN) at resolutions of 3.9 and 3.6 angstroms, respectively, as determined by cryo-electron microscopy. Ptch1 comprises two interacting extracellular domains, ECD1 and ECD2, and 12 transmembrane segments (TMs), with TMs 2 to 6 constituting the sterol-sensing domain (SSD). Two steroid-shaped densities are resolved in both structures, one enclosed by ECD1/2 and the other in the membrane-facing cavity of the SSD. Structure-guided mutational analysis shows that interaction between ShhN and Ptch1 is steroid-dependent. The structure of a steroid binding-deficient Ptch1 mutant displays pronounced conformational rearrangements. | |||||||||
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 | 分子: MolmilJmol/JSmol |
-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 6dmo.cif.gz | 196.8 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb6dmo.ent.gz | 153.2 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 6dmo.json.gz | ツリー表示 | PDBx/mmJSON形式 | |
その他 | その他のダウンロード |
-検証レポート
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/dm/6dmo ftp://data.pdbj.org/pub/pdb/validation_reports/dm/6dmo | HTTPS FTP |
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-関連構造データ
-リンク
-集合体
登録構造単位 |
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1 |
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-要素
#1: タンパク質 | 分子量: 150266.656 Da / 分子数: 1 / 変異: L282Q, T500F, P504L / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: PTCH1, PTCH / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: Q13635 |
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#2: 多糖 | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose |
#3: 糖 | ChemComp-NAG / |
-実験情報
-実験
実験 | 手法: 電子顕微鏡法 |
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EM実験 | 試料の集合状態: PARTICLE / 3次元再構成法: 単粒子再構成法 |
-試料調製
構成要素 | 名称: Patch1 with L282Q/T500F/P504L mutations / タイプ: ORGANELLE OR CELLULAR COMPONENT / Entity ID: #1 / 由来: RECOMBINANT |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
由来(組換発現) | 生物種: Homo sapiens (ヒト) |
緩衝液 | pH: 8 |
試料 | 濃度: 15 mg/ml / 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES |
急速凍結 | 凍結剤: ETHANE |
-電子顕微鏡撮影
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
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顕微鏡 | モデル: FEI TITAN KRIOS |
電子銃 | 電子線源: FIELD EMISSION GUN / 加速電圧: 300 kV / 照射モード: FLOOD BEAM |
電子レンズ | モード: BRIGHT FIELDBright-field microscopy |
撮影 | 電子線照射量: 50 e/Å2 / 検出モード: SUPER-RESOLUTION フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) |
-解析
ソフトウェア | 名称: PHENIX / バージョン: 1.13_2998: / 分類: 精密化 | |||||||||||||||
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EMソフトウェア |
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CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | |||||||||||||||
3次元再構成 | 解像度: 4.1 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 154721 / 対称性のタイプ: POINT |