+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-10311 | |||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
タイトル | Human insulin receptor ectodomain bound by several insulins in an intermediate state | |||||||||||||||
マップデータ | manually filtered, sharpened and masked map. In manuscript labeled as "intermediate state". On different origin as the other maps. | |||||||||||||||
試料 |
| |||||||||||||||
機能・相同性 | 機能・相同性情報 regulation of female gonad development / positive regulation of meiotic cell cycle / positive regulation of developmental growth / insulin-like growth factor II binding / male sex determination / exocrine pancreas development / insulin receptor complex / insulin-like growth factor I binding / insulin receptor activity / positive regulation of protein-containing complex disassembly ...regulation of female gonad development / positive regulation of meiotic cell cycle / positive regulation of developmental growth / insulin-like growth factor II binding / male sex determination / exocrine pancreas development / insulin receptor complex / insulin-like growth factor I binding / insulin receptor activity / positive regulation of protein-containing complex disassembly / cargo receptor activity / dendritic spine maintenance / insulin binding / negative regulation of NAD(P)H oxidase activity / negative regulation of glycogen catabolic process / PTB domain binding / adrenal gland development / positive regulation of nitric oxide mediated signal transduction / negative regulation of fatty acid metabolic process / activation of protein kinase activity / negative regulation of feeding behavior / Signaling by Insulin receptor / IRS activation / Insulin processing / neuronal cell body membrane / regulation of protein secretion / positive regulation of peptide hormone secretion / positive regulation of receptor internalization / positive regulation of respiratory burst / negative regulation of acute inflammatory response / Regulation of gene expression in beta cells / amyloid-beta clearance / alpha-beta T cell activation / transport across blood-brain barrier / regulation of amino acid metabolic process / regulation of embryonic development / negative regulation of respiratory burst involved in inflammatory response / insulin receptor substrate binding / negative regulation of protein secretion / positive regulation of dendritic spine maintenance / positive regulation of glycogen biosynthetic process / epidermis development / Synthesis, secretion, and deacylation of Ghrelin / regulation of protein localization to plasma membrane / fatty acid homeostasis / negative regulation of gluconeogenesis / negative regulation of lipid catabolic process / Signal attenuation / FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes / COPI-mediated anterograde transport / phosphatidylinositol 3-kinase binding / heart morphogenesis / positive regulation of lipid biosynthetic process / positive regulation of insulin receptor signaling pathway / negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway / negative regulation of reactive oxygen species biosynthetic process / nitric oxide-cGMP-mediated signaling / positive regulation of protein autophosphorylation / insulin-like growth factor receptor binding / transport vesicle / Insulin receptor recycling / dendrite membrane / neuron projection maintenance / endoplasmic reticulum-Golgi intermediate compartment membrane / positive regulation of protein metabolic process / positive regulation of brown fat cell differentiation / NPAS4 regulates expression of target genes / activation of protein kinase B activity / positive regulation of glycolytic process / Insulin receptor signalling cascade / positive regulation of mitotic nuclear division / receptor-mediated endocytosis / positive regulation of nitric-oxide synthase activity / learning / acute-phase response / positive regulation of cytokine production / positive regulation of long-term synaptic potentiation / cognition / Regulation of insulin secretion / endosome lumen / positive regulation of D-glucose import / positive regulation of protein secretion / negative regulation of proteolysis / positive regulation of cell differentiation / regulation of transmembrane transporter activity / insulin receptor binding / positive regulation of MAP kinase activity / wound healing / negative regulation of protein catabolic process / receptor protein-tyrosine kinase / caveola / regulation of synaptic plasticity / hormone activity / cellular response to growth factor stimulus / receptor internalization / memory / positive regulation of neuron projection development / peptidyl-tyrosine phosphorylation / cellular response to insulin stimulus / positive regulation of protein localization to nucleus 類似検索 - 分子機能 | |||||||||||||||
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: 5.0 Å | |||||||||||||||
データ登録者 | Gutmann T / Schaefer IB / Poojari C / Brankatschk B / Vattulainen I / Strauss M / Coskun U | |||||||||||||||
資金援助 | ドイツ, フィンランド, 4件
| |||||||||||||||
引用 | ジャーナル: J Cell Biol / 年: 2020 タイトル: Cryo-EM structure of the complete and ligand-saturated insulin receptor ectodomain. 著者: Theresia Gutmann / Ingmar B Schäfer / Chetan Poojari / Beate Brankatschk / Ilpo Vattulainen / Mike Strauss / Ünal Coskun / 要旨: Glucose homeostasis and growth essentially depend on the hormone insulin engaging its receptor. Despite biochemical and structural advances, a fundamental contradiction has persisted in the current ...Glucose homeostasis and growth essentially depend on the hormone insulin engaging its receptor. Despite biochemical and structural advances, a fundamental contradiction has persisted in the current understanding of insulin ligand-receptor interactions. While biochemistry predicts two distinct insulin binding sites, 1 and 2, recent structural analyses have resolved only site 1. Using a combined approach of cryo-EM and atomistic molecular dynamics simulation, we present the structure of the entire dimeric insulin receptor ectodomain saturated with four insulin molecules. Complementing the previously described insulin-site 1 interaction, we present the first view of insulin bound to the discrete insulin receptor site 2. Insulin binding stabilizes the receptor ectodomain in a T-shaped conformation wherein the membrane-proximal domains converge and contact each other. These findings expand the current models of insulin binding to its receptor and of its regulation. In summary, we provide the structural basis for a comprehensive description of ligand-receptor interactions that ultimately will inform new approaches to structure-based drug design. #1: ジャーナル: Biorxiv / 年: 2019 タイトル: Cryo-EM structure of the complete and ligand-saturated insulin receptor ectodomain 著者: Gutmann T / Schafer I / Poojari C / Brankatschk B / Vattulainen I / Strauss M / Coskun U | |||||||||||||||
履歴 |
|
-構造の表示
ムービー |
ムービービューア |
---|---|
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_10311.map.gz | 3.4 MB | EMDBマップデータ形式 | |
---|---|---|---|---|
ヘッダ (付随情報) | emd-10311-v30.xml emd-10311.xml | 20.7 KB 20.7 KB | 表示 表示 | EMDBヘッダ |
FSC (解像度算出) | emd_10311_fsc.xml | 10.3 KB | 表示 | FSCデータファイル |
画像 | emd_10311.png | 124.7 KB | ||
マスクデータ | emd_10311_msk_1.map | 91.1 MB | マスクマップ | |
その他 | emd_10311_additional.map.gz emd_10311_additional_1.map.gz emd_10311_half_map_1.map.gz emd_10311_half_map_2.map.gz | 5.4 MB 5.4 MB 71.3 MB 71.3 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-10311 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-10311 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_10311_validation.pdf.gz | 362.9 KB | 表示 | EMDB検証レポート |
---|---|---|---|---|
文書・詳細版 | emd_10311_full_validation.pdf.gz | 362 KB | 表示 | |
XML形式データ | emd_10311_validation.xml.gz | 16.8 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-10311 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-10311 | HTTPS FTP |
-関連構造データ
-リンク
EMDBのページ | EMDB (EBI/PDBe) / EMDataResource |
---|---|
「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_10311.map.gz / 形式: CCP4 / 大きさ: 91.1 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
注釈 | manually filtered, sharpened and masked map. In manuscript labeled as "intermediate state". On different origin as the other maps. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
投影像・断面図 | 画像のコントロール
画像は Spider により作成 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 1.06 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
密度 |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
CCP4マップ ヘッダ情報:
|
-添付データ
-マスク #1
ファイル | emd_10311_msk_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
投影像・断面図 |
| ||||||||||||
密度ヒストグラム |
-追加マップ: automatically filtered, sharpened and masked map. In manuscript...
ファイル | emd_10311_additional.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
注釈 | automatically filtered, sharpened and masked map. In manuscript labeled as "intermediate state". | ||||||||||||
投影像・断面図 |
| ||||||||||||
密度ヒストグラム |
-追加マップ: automatically filtered, sharpened and masked map. In manuscript...
ファイル | emd_10311_additional_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
注釈 | automatically filtered, sharpened and masked map. In manuscript labeled as "intermediate state". | ||||||||||||
投影像・断面図 |
| ||||||||||||
密度ヒストグラム |
-ハーフマップ: half-map 1 used as input for postprocessing to...
ファイル | emd_10311_half_map_1.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
注釈 | half-map 1 used as input for postprocessing to generate the main map (post Bayesian polishing and 3D refinement) | ||||||||||||
投影像・断面図 |
| ||||||||||||
密度ヒストグラム |
-ハーフマップ: half-map 2 used as input for postprocessing to...
ファイル | emd_10311_half_map_2.map | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
注釈 | half-map 2 used as input for postprocessing to generate the main map (post Bayesian polishing and 3D refinement) | ||||||||||||
投影像・断面図 |
| ||||||||||||
密度ヒストグラム |
-試料の構成要素
-全体 : human insulin receptor ectodomain bound by several insulins in an...
全体 | 名称: human insulin receptor ectodomain bound by several insulins in an intermediate state |
---|---|
要素 |
|
-超分子 #1: human insulin receptor ectodomain bound by several insulins in an...
超分子 | 名称: human insulin receptor ectodomain bound by several insulins in an intermediate state タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: all |
---|---|
由来(天然) | 生物種: Homo sapiens (ヒト) |
組換発現 | 生物種: Homo sapiens (ヒト) |
分子量 | 実験値: 375 KDa |
-分子 #1: human insulin receptor ectodomain
分子 | 名称: human insulin receptor ectodomain / タイプ: protein_or_peptide / ID: 1 / 光学異性体: LEVO |
---|---|
由来(天然) | 生物種: Homo sapiens (ヒト) |
組換発現 | 生物種: Homo sapiens (ヒト) |
配列 | 文字列: HLYPGEVCPG MDIRNNLTRL HELENCSVIE GHLQILLMFK TRPEDFRDLS FPKLIMITDY LLLFRVYGLE SLKDLFPNL TVIRGSRLFF NYALVIFEMV HLKELGLYNL MNITRGSVRI EKNNELCYLA TIDWSRILDS V EDNYIVLN KDDNEECGDI CPGTAKGKTN ...文字列: HLYPGEVCPG MDIRNNLTRL HELENCSVIE GHLQILLMFK TRPEDFRDLS FPKLIMITDY LLLFRVYGLE SLKDLFPNL TVIRGSRLFF NYALVIFEMV HLKELGLYNL MNITRGSVRI EKNNELCYLA TIDWSRILDS V EDNYIVLN KDDNEECGDI CPGTAKGKTN CPATVINGQF VERCWTHSHC QKVCPTICKS HGCTAEGLCC HS ECLGNCS QPDDPTKCVA CRNFYLDGRC VETCPPPYYH FQDWRCVNFS FCQDLHHKCK NSRRQGCHQY VIH NNKCIP ECPSGYTMNS SNLLCTPCLG PCPKVCHLLE GEKTIDSVTS AQELRGCTVI NGSLIINIRG GNNL AAELE ANLGLIEEIS GYLKIRRSYA LVSLSFFRKL RLIRGETLEI GNYSFYALDN QNLRQLWDWS KHNLT ITQG KLFFHYNPKL CLSEIHKMEE VSGTKGRQER NDIALKTNGD QASCENELLK FSYIRTSFDK ILLRWE PYW PPDFRDLLGF MLFYKEAPYQ NVTEFDGQDA CGSNSWTVVD IDPPLRSNDP KSQNHPGWLM RGLKPWT QY AIFVKTLVTF SDERRTYGAK SDIIYVQTDA TNPSVPLDPI SVSNSSSQII LKWKPPSDPN GNITHYLV F WERQAEDSEL FELDYCLKGL KLPSRTWSPP FESEDSQKHN QSEYEDSAGE CCSCPKTDSQ ILKELEESS FRKTFEDYLH NVVFVPRPS HRPFEKVVNK ESLVISGLRH FTGYRIELQA CNQDTPEERC SVAAYVSART MPEAKADDIV GPVTHEIFEN NVVHLMWQE PKEPNGLIVL YEVSYRRYGD EELHLCVSRK HFALERGCRL RGLSPGNYSV RIRATSLAGN G SWTEPTYF YVTDYLDVPS NIAK |
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
---|---|
解析 | 単粒子再構成法 |
試料の集合状態 | particle |
-試料調製
緩衝液 | pH: 7.5 |
---|---|
凍結 | 凍結剤: ETHANE-PROPANE |
-電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
---|---|
撮影 | フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) 検出モード: COUNTING / 撮影したグリッド数: 1 / 実像数: 51 / 平均露光時間: 10.2 sec. / 平均電子線量: 55.0 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: FIELD EMISSION GUN |
電子光学系 | 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELD |
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 |