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基本情報
登録情報 | データベース: EMDB / ID: EMD-21418 | |||||||||
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タイトル | Leg region of the closed conformation of the human type 1 insulin-like growth factor receptor ectodomain in complex with human insulin-like growth factor II | |||||||||
![]() | leg part of the close conformation | |||||||||
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機能・相同性 | ![]() cardiac atrium development / negative regulation of cholangiocyte apoptotic process / insulin-like growth factor receptor activity / positive regulation of steroid hormone biosynthetic process / protein kinase complex / Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R) / IRS-related events triggered by IGF1R / insulin-like growth factor binding / protein transporter activity / negative regulation of muscle cell apoptotic process ...cardiac atrium development / negative regulation of cholangiocyte apoptotic process / insulin-like growth factor receptor activity / positive regulation of steroid hormone biosynthetic process / protein kinase complex / Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R) / IRS-related events triggered by IGF1R / insulin-like growth factor binding / protein transporter activity / negative regulation of muscle cell apoptotic process / cellular response to progesterone stimulus / positive regulation of DNA metabolic process / protein localization to nuclear periphery / FCERI mediated MAPK activation / cellular response to zinc ion starvation / cellular response to aldosterone / Activation of the AP-1 family of transcription factors / response to amino acid starvation / mediator complex binding / negative regulation of ribosomal protein gene transcription by RNA polymerase II / positive regulation of cellular response to amino acid starvation / insulin receptor complex / cellular response to testosterone stimulus / negative regulation of hepatocyte apoptotic process / insulin-like growth factor I binding / insulin receptor activity / transcytosis / nitrogen catabolite activation of transcription from RNA polymerase II promoter / alphav-beta3 integrin-IGF-1-IGF1R complex / response to alkaloid / Oxidative Stress Induced Senescence / cellular response to angiotensin / positive regulation of protein-containing complex disassembly / dendritic spine maintenance / cellular response to insulin-like growth factor stimulus / insulin binding / response to L-glutamate / negative regulation of MAPK cascade / establishment of cell polarity / positive regulation of axon regeneration / amyloid-beta clearance / positive regulation of osteoblast proliferation / positive regulation of cytokinesis / Respiratory syncytial virus (RSV) attachment and entry / TFIID-class transcription factor complex binding / regulation of JNK cascade / insulin receptor substrate binding / estrous cycle / G-protein alpha-subunit binding / response to vitamin E / positive regulation of RNA polymerase II transcription preinitiation complex assembly / positive regulation of transcription initiation by RNA polymerase II / amino acid biosynthetic process / SHC-related events triggered by IGF1R / cellular response to nutrient levels / phosphatidylinositol 3-kinase binding / peptidyl-tyrosine autophosphorylation / cellular response to transforming growth factor beta stimulus / T-tubule / phosphatidylinositol 3-kinase/protein kinase B signal transduction / cellular response to amino acid starvation / cellular response to dexamethasone stimulus / cerebellum development / axonogenesis / insulin-like growth factor receptor signaling pathway / caveola / cellular response to estradiol stimulus / hippocampus development / cellular response to glucose stimulus / positive regulation of smooth muscle cell proliferation / insulin receptor binding / response to nicotine / receptor protein-tyrosine kinase / cellular response to mechanical stimulus / RNA polymerase II transcription regulator complex / cellular response to amyloid-beta / cellular senescence / insulin receptor signaling pathway / positive regulation of cold-induced thermogenesis / DNA-binding transcription activator activity, RNA polymerase II-specific / protein tyrosine kinase activity / response to ethanol / RNA polymerase II-specific DNA-binding transcription factor binding / transcription regulator complex / sequence-specific DNA binding / positive regulation of MAPK cascade / protein autophosphorylation / Extra-nuclear estrogen signaling / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / receptor complex / DNA-binding transcription factor activity, RNA polymerase II-specific / intracellular signal transduction / positive regulation of cell migration / immune response / RNA polymerase II cis-regulatory region sequence-specific DNA binding / DNA-binding transcription factor activity / axon / intracellular membrane-bounded organelle / neuronal cell body / chromatin binding 類似検索 - 分子機能 | |||||||||
生物種 | ![]() ![]() ![]() | |||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 4.21 Å | |||||||||
![]() | Xu Y / Kirk NS / Lawrence MC / Croll TI | |||||||||
資金援助 | ![]() ![]()
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![]() | ![]() タイトル: How IGF-II Binds to the Human Type 1 Insulin-like Growth Factor Receptor. 著者: Yibin Xu / Nicholas S Kirk / Hariprasad Venugopal / Mai B Margetts / Tristan I Croll / Jarrod J Sandow / Andrew I Webb / Carlie A Delaine / Briony E Forbes / Michael C Lawrence / ![]() ![]() 要旨: Human type 1 insulin-like growth factor receptor (IGF-1R) signals chiefly in response to the binding of insulin-like growth factor I. Relatively little is known about the role of insulin-like growth ...Human type 1 insulin-like growth factor receptor (IGF-1R) signals chiefly in response to the binding of insulin-like growth factor I. Relatively little is known about the role of insulin-like growth factor II signaling via IGF-1R, despite the affinity of insulin-like growth factor II for IGF-1R being within an order of magnitude of that of insulin-like growth factor I. Here, we describe the cryoelectron microscopy structure of insulin-like growth factor II bound to a leucine-zipper-stabilized IGF-1R ectodomain, determined in two conformations to a maximum average resolution of 3.2 Å. The two conformations differ in the relative separation of their respective points of membrane entry, and comparison with the structure of insulin-like growth factor I bound to IGF-1R reveals long-suspected differences in the way in which the critical C domain of the respective growth factors interact with IGF-1R. | |||||||||
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「今月の分子」の関連する項目 |
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注釈 | leg part of the close conformation | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 1.06 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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試料の構成要素
-全体 : Leg region of the open-leg conformation of the human type 1 insul...
全体 | 名称: Leg region of the open-leg conformation of the human type 1 insulin-like growth factor receptor ectodomain in complex with human insulin-like growth factor II |
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要素 |
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-超分子 #1: Leg region of the open-leg conformation of the human type 1 insul...
超分子 | 名称: Leg region of the open-leg conformation of the human type 1 insulin-like growth factor receptor ectodomain in complex with human insulin-like growth factor II タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: all |
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由来(天然) | 生物種: ![]() |
分子量 | 理論値: 250 KDa |
-分子 #1: Leucine-zippered human type 1 insulin-like growth factor receptor...
分子 | 名称: Leucine-zippered human type 1 insulin-like growth factor receptor ectodomain 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: ![]() ![]() 株: ATCC 204508 / S288c |
分子量 | 理論値: 108.937242 KDa |
組換発現 | 生物種: ![]() ![]() |
配列 | 文字列: EICGPGIDIR NDYQQLKRLE NCTVIEGYLH ILLISKAEDY RSYRFPKLTV ITEYLLLFRV AGLESLGDLF PNLTVIRGWK LFYNYALVI FEMTNLKDIG LYNLRNITRG AIRIEKNADL CYLSTVDWSL ILDAVSNNYI VGNKPPKECG DLCPGTMEEK P MCEKTTIN ...文字列: EICGPGIDIR NDYQQLKRLE NCTVIEGYLH ILLISKAEDY RSYRFPKLTV ITEYLLLFRV AGLESLGDLF PNLTVIRGWK LFYNYALVI FEMTNLKDIG LYNLRNITRG AIRIEKNADL CYLSTVDWSL ILDAVSNNYI VGNKPPKECG DLCPGTMEEK P MCEKTTIN NEYNYRCWTT NRCQKMCPST CGKRACTENN ECCHPECLGS CSAPDNDTAC VACRHYYYAG VCVPACPPNT YR FEGWRCV DRDFCANILS AESSDSEGFV IHDGECMQEC PSGFIRNGSQ SMYCIPCEGP CPKVCEEEKK TKTIDSVTSA QML QGCTIF KGNLLINIRR GNNIASELEN FMGLIEVVTG YVKIRHSHAL VSLSFLKNLR LILGEEQLEG NYSFYVLDNQ NLQQ LWDWD HRNLTIKAGK MYFAFNPKLC VSEIYRMEEV TGTKGRQSKG DINTRNNGER ASCESDVLHF TSTTTSKNRI IITWH RYRP PDYRDLISFT VYYKEAPFKN VTEYDGQDAC GSNSWNMVDV DLPPNKDVEP GILLHGLKPW TQYAVYVKAV TLTMVE NDH IRGAKSEILY IRTNASVPSI PLDVLSASNS SSQLIVKWNP PSLPNGNLSY YIVRWQRQPQ DGYLYRHNYC SKDKIPI RK YADGTIDIEE VTENPKTEVC GGEKGPCCAC PKTEAEKQAE KEEAEYRKVF ENFLHNSIFV PRPERKRRDV MQVANTTM S SRSRNTTAAD TYNITDPEEL ETEYPFFESR VDNKERTVIS NLRPFTLYRI DIHSCNHEAE KLGCSASNFV FARTMPAEG ADDIPGPVTW EPRPENSIFL KWPEPENPNG LILMYEIKYG SQVEDQRECV SRQEYRKYGG AKLNRLNPGN YTARIQATSL SGNGSWTDP VFFYVQAKTG YENFIHRMKQ LEDKVEELLS KNYHLENEVA RLKKLVGERS SSEQKLISEE DLN |
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
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![]() | 単粒子再構成法 |
試料の集合状態 | particle |
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試料調製
濃度 | 0.1 mg/mL | ||||||||||
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緩衝液 | pH: 7.5 構成要素:
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グリッド | モデル: Quantifoil, UltrAuFoil, R1.2/1.3 / 材質: GOLD / メッシュ: 300 / 前処理 - タイプ: GLOW DISCHARGE / 詳細: 15mA current | ||||||||||
凍結 | 凍結剤: ETHANE / チャンバー内湿度: 100 % / チャンバー内温度: 277 K / 装置: FEI VITROBOT MARK IV | ||||||||||
詳細 | IGFII:IGF-1R molar ratio 1.5:1 |
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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 |
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 / デジタル化 - 画像ごとのフレーム数: 1-50 / 撮影したグリッド数: 1 / 実像数: 4585 / 平均露光時間: 10.0 sec. / 平均電子線量: 50.0 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: ![]() |
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 |
試料ステージ | ホルダー冷却材: NITROGEN |
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |
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画像解析
-原子モデル構築 1
初期モデル | PDB ID: |
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詳細 | UCSF Chimera was used for the initial fitting and ISOLDE v 1.03b was using for flexible fitting. |
精密化 | 空間: REAL / プロトコル: FLEXIBLE FIT |
得られたモデル | ![]() PDB-6vwj: |