+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-0246 | |||||||||||||||
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タイトル | Leucine-zippered human insulin receptor ectodomain with single bound insulin - "lower" membrane-proximal part | |||||||||||||||
マップデータ | insulin bound to insulin receptor ectodomain - "lower" membrane-proximal part | |||||||||||||||
試料 |
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機能・相同性 | 機能・相同性情報 regulation of female gonad development / positive regulation of meiotic cell cycle / protein localization to nuclear periphery / FCERI mediated MAPK activation / Activation of the AP-1 family of transcription factors / response to amino acid starvation / insulin-like growth factor II binding / positive regulation of developmental growth / mediator complex binding / negative regulation of ribosomal protein gene transcription by RNA polymerase II ...regulation of female gonad development / positive regulation of meiotic cell cycle / protein localization to nuclear periphery / FCERI mediated MAPK activation / Activation of the AP-1 family of transcription factors / response to amino acid starvation / insulin-like growth factor II binding / positive regulation of developmental growth / mediator complex binding / negative regulation of ribosomal protein gene transcription by RNA polymerase II / positive regulation of cellular response to amino acid starvation / male sex determination / exocrine pancreas development / insulin receptor complex / insulin-like growth factor I binding / insulin receptor activity / nitrogen catabolite activation of transcription from RNA polymerase II promoter / Oxidative Stress Induced Senescence / positive regulation of protein-containing complex disassembly / cargo receptor activity / dendritic spine maintenance / insulin binding / PTB domain binding / adrenal gland development / Signaling by Insulin receptor / IRS activation / activation of protein kinase activity / neuronal cell body membrane / amyloid-beta clearance / positive regulation of respiratory burst / positive regulation of receptor internalization / TFIID-class transcription factor complex binding / regulation of embryonic development / insulin receptor substrate binding / transport across blood-brain barrier / positive regulation of glycogen biosynthetic process / positive regulation of RNA polymerase II transcription preinitiation complex assembly / epidermis development / positive regulation of transcription initiation by RNA polymerase II / amino acid biosynthetic process / cellular response to nutrient levels / Signal attenuation / phosphatidylinositol 3-kinase binding / heart morphogenesis / Insulin receptor recycling / insulin-like growth factor receptor binding / dendrite membrane / neuron projection maintenance / activation of protein kinase B activity / positive regulation of glycolytic process / cellular response to amino acid starvation / positive regulation of mitotic nuclear division / Insulin receptor signalling cascade / receptor-mediated endocytosis / positive regulation of MAP kinase activity / learning / caveola / positive regulation of glucose import / receptor protein-tyrosine kinase / peptidyl-tyrosine phosphorylation / cellular response to insulin stimulus / receptor internalization / RNA polymerase II transcription regulator complex / memory / cellular response to growth factor stimulus / male gonad development / positive regulation of nitric oxide biosynthetic process / glucose homeostasis / late endosome / insulin receptor signaling pathway / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling / amyloid-beta binding / DNA-binding transcription activator activity, RNA polymerase II-specific / protein tyrosine kinase activity / transcription regulator complex / sequence-specific DNA binding / protein autophosphorylation / RNA polymerase II-specific DNA-binding transcription factor binding / receptor complex / positive regulation of MAPK cascade / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / endosome membrane / DNA-binding transcription factor activity, RNA polymerase II-specific / lysosome / positive regulation of cell migration / intracellular signal transduction / positive regulation of protein phosphorylation / symbiont entry into host cell / RNA polymerase II cis-regulatory region sequence-specific DNA binding / protein domain specific binding / DNA-binding transcription factor activity / G protein-coupled receptor signaling pathway / protein phosphorylation / external side of plasma membrane / axon / chromatin binding / positive regulation of cell population proliferation / positive regulation of DNA-templated transcription / regulation of DNA-templated transcription / protein-containing complex binding 類似検索 - 分子機能 | |||||||||||||||
生物種 | Homo sapiens (ヒト) / Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (パン酵母) | |||||||||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 4.2 Å | |||||||||||||||
データ登録者 | Weis F / Menting JG / Margetts MB / Chan SJ / Xu Y / Tennagels N / Wohlfart P / Langer T / Mueller CW / Dreyer MK / Lawrence MC | |||||||||||||||
資金援助 | オーストラリア, 米国, 4件
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引用 | ジャーナル: Nat Commun / 年: 2018 タイトル: The signalling conformation of the insulin receptor ectodomain. 著者: Felix Weis / John G Menting / Mai B Margetts / Shu Jin Chan / Yibin Xu / Norbert Tennagels / Paulus Wohlfart / Thomas Langer / Christoph W Müller / Matthias K Dreyer / Michael C Lawrence / 要旨: Understanding the structural biology of the insulin receptor and how it signals is of key importance in the development of insulin analogs to treat diabetes. We report here a cryo-electron microscopy ...Understanding the structural biology of the insulin receptor and how it signals is of key importance in the development of insulin analogs to treat diabetes. We report here a cryo-electron microscopy structure of a single insulin bound to a physiologically relevant, high-affinity version of the receptor ectodomain, the latter generated through attachment of C-terminal leucine zipper elements to overcome the conformational flexibility associated with ectodomain truncation. The resolution of the cryo-electron microscopy maps is 3.2 Å in the insulin-binding region and 4.2 Å in the membrane-proximal region. The structure reveals how the membrane proximal domains of the receptor come together to effect signalling and how insulin's negative cooperativity of binding likely arises. Our structure further provides insight into the high affinity of certain super-mitogenic insulins. Together, these findings provide a new platform for insulin analog investigation and design. | |||||||||||||||
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 | EMマップ: SurfViewMolmilJmol/JSmol |
添付画像 |
-ダウンロードとリンク
-EMDBアーカイブ
マップデータ | emd_0246.map.gz | 2.5 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-0246-v30.xml emd-0246.xml | 17.4 KB 17.4 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_0246.png | 110.5 KB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-0246 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-0246 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_0246_validation.pdf.gz | 295.3 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_0246_full_validation.pdf.gz | 294.8 KB | 表示 | |
XML形式データ | emd_0246_validation.xml.gz | 6.4 KB | 表示 | |
CIF形式データ | emd_0246_validation.cif.gz | 7.2 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-0246 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-0246 | HTTPS FTP |
-関連構造データ
-リンク
EMDBのページ | EMDB (EBI/PDBe) / EMDataResource |
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「今月の分子」の関連する項目 |
-マップ
ファイル | ダウンロード / ファイル: emd_0246.map.gz / 形式: CCP4 / 大きさ: 91.1 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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注釈 | insulin bound to insulin receptor ectodomain - "lower" membrane-proximal part | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 1.04 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
CCP4マップ ヘッダ情報:
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-添付データ
-試料の構成要素
-全体 : Leucine zippered human insulin receptor ectodomain (IR-A isoform,...
全体 | 名称: Leucine zippered human insulin receptor ectodomain (IR-A isoform, "deltabeta" mutant) in complex with insulin and two Fv 83-7 modules : "lower" membrane-proximal part |
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要素 |
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-超分子 #1: Leucine zippered human insulin receptor ectodomain (IR-A isoform,...
超分子 | 名称: Leucine zippered human insulin receptor ectodomain (IR-A isoform, "deltabeta" mutant) in complex with insulin and two Fv 83-7 modules : "lower" membrane-proximal part タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1 詳細: Note: Attached to the leucine-zippered insulin receptor ectodomain are two Fv 83-7 modules. One of these is present within this map volume but it is very poorly ordered and thus left ...詳細: Note: Attached to the leucine-zippered insulin receptor ectodomain are two Fv 83-7 modules. One of these is present within this map volume but it is very poorly ordered and thus left completely unmodelled. See the manuscript for further details. |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
組換発現 | 生物種: Cricetulus griseus (モンゴルキヌゲネズミ) 組換細胞: Lec8 / 組換プラスミド: pEE14 |
-分子 #1: Insulin receptor,Insulin receptor,General control protein GCN4
分子 | 名称: Insulin receptor,Insulin receptor,General control protein GCN4 タイプ: protein_or_peptide / ID: 1 / コピー数: 2 / 光学異性体: LEVO / EC番号: receptor protein-tyrosine kinase |
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由来(天然) | 生物種: Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (パン酵母) 株: ATCC 204508 / S288c |
分子量 | 理論値: 106.728211 KDa |
組換発現 | 生物種: Cricetulus griseus (モンゴルキヌゲネズミ) |
配列 | 文字列: HLYPGEVCPG MDIRNNLTRL HELENCSVIE GHLQILLMFK TRPEDFRDLS FPKLIMITDY LLLFRVYGLE SLKDLFPNLT VIRGSRLFF NYALVIFEMV HLKELGLYNL MNITRGSVRI EKNNELCYLA TIDWSRILDS VEDNHIVLNK DDNEECGDIC P GTAKGKTN ...文字列: HLYPGEVCPG MDIRNNLTRL HELENCSVIE GHLQILLMFK TRPEDFRDLS FPKLIMITDY LLLFRVYGLE SLKDLFPNLT VIRGSRLFF NYALVIFEMV HLKELGLYNL MNITRGSVRI EKNNELCYLA TIDWSRILDS VEDNHIVLNK DDNEECGDIC P GTAKGKTN CPATVINGQF VERCWTHSHC QKVCPTICKS HGCTAEGLCC HSECLGNCSQ PDDPTKCVAC RNFYLDGRCV ET CPPPYYH FQDWRCVNFS FCQDLHHKCK NSRRQGCHQY VIHNNKCIPE CPSGYTMNSS NLLCTPCLGP CPKVCHLLEG EKT IDSVTS AQELRGCTVI NGSLIINIRG GNNLAAELEA NLGLIEEISG YLKIRRSYAL VSLSFFRKLR LIRGETLEIG NYSF YALDN QNLRQLWDWS KHNLTTTQGK LFFHYNPKLC LSEIHKMEEV SGTKGRQERN DIALKTNGDK ASCENELLKF SYIRT SFDK ILLRWEPYWP PDFRDLLGFM LFYKEAPYQN VTEFDGQDAC GSNSWTVVDI DPPLRSNDPK SQNHPGWLMR GLKPWT QYA IFVKTLVTFS DERRTYGAKS DIIYVQTDAT NPSVPLDPIS VSNSSSQIIL KWKPPSDPNG NITHYLVFWE RQAEDSE LF ELDYCLKGLK LPSRTWSPPF ESEDSQKHNQ SEYEDSAGEC CSCPKTDSQI LKELEESSFR KTFEDYLHNV VFVPRPSR K RRSLGDVGNA GNNEEHRPFE KVVNKESLVI SGLRHFTGYR IELQACNQDT PEERCSVAAY VSARTMPEAK ADDIVGPVT HEIFENNVVH LMWQEPKEPN GLIVLYEVSY RRYGDEELHL CVSRKHFALE RGCRLRGLSP GNYSVRIRAT SLAGNGSWTE PTYFYVTDY LDVPSNIARM KQLEDKVEEL LSKNYHLENE VARLKKLVGE R |
-分子 #2: 2-acetamido-2-deoxy-beta-D-glucopyranose
分子 | 名称: 2-acetamido-2-deoxy-beta-D-glucopyranose / タイプ: ligand / ID: 2 / コピー数: 6 / 式: NAG |
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分子量 | 理論値: 221.208 Da |
Chemical component information | ChemComp-NAG: |
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
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解析 | 単粒子再構成法 |
試料の集合状態 | particle |
-試料調製
濃度 | 0.094 mg/mL | |||||||||
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緩衝液 | pH: 7.5 構成要素:
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凍結 | 凍結剤: ETHANE / チャンバー内湿度: 100 % / チャンバー内温度: 283.15 K / 装置: FEI VITROBOT MARK IV |
-電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
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特殊光学系 | エネルギーフィルター - 名称: GIF Quantum LS / エネルギーフィルター - スリット幅: 20 eV |
撮影 | フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) 検出モード: SUPER-RESOLUTION / デジタル化 - 画像ごとのフレーム数: 1-20 / 撮影したグリッド数: 1 / 実像数: 2287 / 平均露光時間: 16.0 sec. / 平均電子線量: 1.85 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: FIELD EMISSION GUN |
電子光学系 | C2レンズ絞り径: 50.0 µm / 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELD / Cs: 2.7 mm / 最大 デフォーカス(公称値): 2.5 µm / 最小 デフォーカス(公称値): 1.0 µm / 倍率(公称値): 130000 |
試料ステージ | 試料ホルダーモデル: FEI TITAN KRIOS AUTOGRID HOLDER ホルダー冷却材: NITROGEN |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |