+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 6mg8 | ||||||||||||||||||
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タイトル | Structural basis for cholesterol transport-like activity of the Hedgehog receptor Patched | ||||||||||||||||||
要素 | Protein patched homolog 1 | ||||||||||||||||||
キーワード | MEMBRANE PROTEIN (膜タンパク質) / Receptor Membrane protein | ||||||||||||||||||
機能・相同性 | 機能・相同性情報 Ligand-receptor interactions / Activation of SMO / 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 formation / neural tube patterning ...Ligand-receptor interactions / Activation of SMO / 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 formation / neural tube patterning / hedgehog family protein binding / hindlimb morphogenesis / Hedgehog 'on' state / epidermal cell fate specification / spinal cord motor neuron differentiation / prostate gland development / negative regulation of cell division / Hedgehog 'off' state / patched binding / limb morphogenesis / somite development / dorsal/ventral neural tube patterning / cellular response to cholesterol / smooth muscle tissue development / pattern specification process / pharyngeal system development / mammary gland duct morphogenesis / mammary gland epithelial cell differentiation / 拘束 (生物学) / mammary gland development / commissural neuron axon guidance / metanephric collecting duct development / dorsal/ventral pattern formation / embryonic limb morphogenesis / regulation of growth / cholesterol binding / negative regulation of multicellular organism growth / branching involved in ureteric bud morphogenesis / positive regulation of epidermal cell differentiation / spermatid development / regulation of mitotic cell cycle / dendritic growth cone / positive regulation of cholesterol efflux / keratinocyte proliferation / negative regulation of keratinocyte proliferation / epidermis development / negative regulation of osteoblast differentiation / embryonic organ development / 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 / cyclin binding / epithelial cell proliferation / stem cell proliferation / neural tube closure / liver regeneration / カベオラ / protein localization to plasma membrane / animal organ morphogenesis / brain development / 繊毛 / protein processing / regulation of protein localization / negative regulation of epithelial cell proliferation / glucose homeostasis / response to estradiol / apical part of cell / heparin binding / regulation of cell population proliferation / midbody / in utero embryonic development / response to xenobiotic stimulus / negative regulation of cell population proliferation / intracellular membrane-bounded organelle / negative regulation of DNA-templated transcription / protein-containing complex binding / perinuclear region of cytoplasm / positive regulation of DNA-templated transcription / ゴルジ体 / negative regulation of transcription by RNA polymerase II / シグナル伝達 / zinc ion binding / extracellular region / 細胞膜 類似検索 - 分子機能 | ||||||||||||||||||
生物種 | Mus musculus (ハツカネズミ) | ||||||||||||||||||
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: 3.6 Å | ||||||||||||||||||
データ登録者 | Zhang, Y. / Bulkley, D. / Xin, Y. / Roberts, K.J. / Asarnow, D.E. / Sharma, A. / Myers, B.R. / Cho, W. / Cheng, Y. / Beachy, P.A. | ||||||||||||||||||
資金援助 | 米国, 5件
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引用 | ジャーナル: Cell / 年: 2018 タイトル: Structural Basis for Cholesterol Transport-like Activity of the Hedgehog Receptor Patched. 著者: Yunxiao Zhang / David P Bulkley / Yao Xin / Kelsey J Roberts / Daniel E Asarnow / Ashutosh Sharma / Benjamin R Myers / Wonhwa Cho / Yifan Cheng / Philip A Beachy / 要旨: Hedgehog protein signals mediate tissue patterning and maintenance by binding to and inactivating their common receptor Patched, a 12-transmembrane protein that otherwise would suppress the activity ...Hedgehog protein signals mediate tissue patterning and maintenance by binding to and inactivating their common receptor Patched, a 12-transmembrane protein that otherwise would suppress the activity of the 7-transmembrane protein Smoothened. Loss of Patched function, the most common cause of basal cell carcinoma, permits unregulated activation of Smoothened and of the Hedgehog pathway. A cryo-EM structure of the Patched protein reveals striking transmembrane domain similarities to prokaryotic RND transporters. A central hydrophobic conduit with cholesterol-like contents courses through the extracellular domain and resembles that used by other RND proteins to transport substrates, suggesting Patched activity in cholesterol transport. Cholesterol activity in the inner leaflet of the plasma membrane is reduced by PTCH1 expression but rapidly restored by Hedgehog stimulation, suggesting that PTCH1 regulates Smoothened by controlling cholesterol availability. | ||||||||||||||||||
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 | 6mg8.cif.gz | 181.9 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb6mg8.ent.gz | 137 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 6mg8.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/mg/6mg8 ftp://data.pdbj.org/pub/pdb/validation_reports/mg/6mg8 | 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: 145357.844 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Mus musculus (ハツカネズミ) / 遺伝子: Ptch1, Ptch / 細胞株 (発現宿主): HEK293 / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: Q61115 | ||
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#2: 化合物 | ChemComp-CLR / 非ポリマーの詳細 | THE AUTHORS STATE THAT THE EXACT IDENTITY OF THE LIGAND IS UNKNOWN. CHOLESTEROL WAS MODELED INTO ...THE AUTHORS STATE THAT THE EXACT IDENTITY OF THE LIGAND IS UNKNOWN. CHOLESTERO | |
-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: Patched1 protein solubilized in amphipol / タイプ: COMPLEX / Entity ID: #1 / 由来: RECOMBINANT |
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分子量 | 値: 0.1452 MDa / 実験値: NO |
由来(天然) | 生物種: Homo sapiens (ヒト) |
由来(組換発現) | 生物種: Homo sapiens (ヒト) / 細胞: HEK293 / プラスミド: BacMam |
緩衝液 | pH: 7.4 |
試料 | 濃度: 0.3 mg/ml / 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES |
試料支持 | グリッドの材料: COPPER / グリッドのサイズ: 400 divisions/in. / グリッドのタイプ: Quantifoil R1.2/1.3 |
急速凍結 | 装置: FEI VITROBOT MARK III / 凍結剤: ETHANE / 湿度: 100 % / 凍結前の試料温度: 23 K |
-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 / Cs: 2.7 mm |
撮影 | 平均露光時間: 8 sec. / 電子線照射量: 38 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) 撮影したグリッド数: 1 / 実像数: 5236 |
画像スキャン | 動画フレーム数/画像: 40 |
-解析
ソフトウェア | 名称: PHENIX / バージョン: dev_2608: / 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 | ||||||||||||||||||||||||||||||||||||
粒子像の選択 | 選択した粒子像数: 378828 詳細: Number of particles selected after rough initial 2D classification | ||||||||||||||||||||||||||||||||||||
対称性 | 点対称性: C1 (非対称) | ||||||||||||||||||||||||||||||||||||
3次元再構成 | 解像度: 3.6 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 245725 / 対称性のタイプ: POINT | ||||||||||||||||||||||||||||||||||||
原子モデル構築 | プロトコル: AB INITIO MODEL / 空間: REAL | ||||||||||||||||||||||||||||||||||||
精密化 | 立体化学のターゲット値: GeoStd + Monomer Library + CDL v1.2 | ||||||||||||||||||||||||||||||||||||
原子変位パラメータ | Biso mean: 91.48 Å2 | ||||||||||||||||||||||||||||||||||||
拘束条件 |
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