+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 6jk8 | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
タイトル | Cryo-EM structure of the full-length human IGF-1R in complex with insulin | ||||||||||||
要素 |
| ||||||||||||
キーワード | SIGNALING PROTEIN / human type 1 insulin-like growth factor receptor / insulin | ||||||||||||
機能・相同性 | 機能・相同性情報 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) / protein transporter activity / IRS-related events triggered by IGF1R / insulin-like growth factor binding / 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) / protein transporter activity / IRS-related events triggered by IGF1R / insulin-like growth factor binding / negative regulation of muscle cell apoptotic process / cellular response to progesterone stimulus / positive regulation of DNA metabolic process / cellular response to zinc ion starvation / cellular response to aldosterone / insulin receptor complex / cellular response to testosterone stimulus / negative regulation of hepatocyte apoptotic process / insulin-like growth factor I binding / insulin receptor activity / transcytosis / alphav-beta3 integrin-IGF-1-IGF1R complex / response to alkaloid / 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 NAD(P)H oxidase activity / negative regulation of glycogen catabolic process / negative regulation of MAPK cascade / positive regulation of nitric oxide mediated signal transduction / negative regulation of fatty acid metabolic process / establishment of cell polarity / negative regulation of feeding behavior / Signaling by Insulin receptor / IRS activation / Insulin processing / positive regulation of axon regeneration / regulation of protein secretion / amyloid-beta clearance / positive regulation of osteoblast proliferation / positive regulation of respiratory burst / positive regulation of peptide hormone secretion / positive regulation of cytokinesis / negative regulation of acute inflammatory response / Regulation of gene expression in beta cells / Respiratory syncytial virus (RSV) attachment and entry / alpha-beta T cell activation / regulation of JNK cascade / regulation of cellular amino acid metabolic process / negative regulation of respiratory burst involved in inflammatory response / insulin receptor substrate binding / positive regulation of dendritic spine maintenance / estrous cycle / positive regulation of glycogen biosynthetic process / G-protein alpha-subunit binding / response to vitamin E / Synthesis, secretion, and deacylation of Ghrelin / negative regulation of protein secretion / regulation of protein localization to plasma membrane / SHC-related events triggered by IGF1R / fatty acid homeostasis / Signal attenuation / negative regulation of lipid catabolic process / FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes / negative regulation of gluconeogenesis / phosphatidylinositol 3-kinase binding / COPI-mediated anterograde transport / positive regulation of lipid biosynthetic process / negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway / negative regulation of reactive oxygen species biosynthetic process / peptidyl-tyrosine autophosphorylation / positive regulation of insulin receptor signaling pathway / nitric oxide-cGMP-mediated signaling / transport vesicle / positive regulation of protein autophosphorylation / cellular response to transforming growth factor beta stimulus / T-tubule / Insulin receptor recycling / neuron projection maintenance / positive regulation of protein metabolic process / NPAS4 regulates expression of target genes / phosphatidylinositol 3-kinase/protein kinase B signal transduction / positive regulation of brown fat cell differentiation / positive regulation of glycolytic process / activation of protein kinase B activity / endoplasmic reticulum-Golgi intermediate compartment membrane / positive regulation of mitotic nuclear division / Insulin receptor signalling cascade / cellular response to dexamethasone stimulus / cerebellum development / axonogenesis / insulin-like growth factor receptor signaling pathway / positive regulation of nitric-oxide synthase activity / positive regulation of cytokine production / positive regulation of long-term synaptic potentiation / caveola / acute-phase response / cellular response to estradiol stimulus 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: 5 Å | ||||||||||||
データ登録者 | Zhang, X. / Yu, D. / Wang, T. | ||||||||||||
資金援助 | 中国, 3件
| ||||||||||||
引用 | ジャーナル: Structure / 年: 2020 タイトル: Visualization of Ligand-Bound Ectodomain Assembly in the Full-Length Human IGF-1 Receptor by Cryo-EM Single-Particle Analysis. 著者: Xi Zhang / Daqi Yu / Jingchuan Sun / Yujie Wu / Junyuan Gong / Xuemei Li / Li Liu / Shan Liu / Jianbo Liu / Yulan Wu / Dongyang Li / Yinping Ma / Xu Han / Yanan Zhu / Zhaolong Wu / Yihua Wang ...著者: Xi Zhang / Daqi Yu / Jingchuan Sun / Yujie Wu / Junyuan Gong / Xuemei Li / Li Liu / Shan Liu / Jianbo Liu / Yulan Wu / Dongyang Li / Yinping Ma / Xu Han / Yanan Zhu / Zhaolong Wu / Yihua Wang / Qi Ouyang / Tao Wang / 要旨: Tyrosine kinase receptor of insulin-like growth factor 1 receptor (IGF-1R) and insulin receptor (IR) bind to hormones, such as insulin, IGF-1, and IGF-2, and transduces the signals across the cell ...Tyrosine kinase receptor of insulin-like growth factor 1 receptor (IGF-1R) and insulin receptor (IR) bind to hormones, such as insulin, IGF-1, and IGF-2, and transduces the signals across the cell membrane. However, the complete structure of the receptor and the signal transduction mechanism remains unclear. Here, we report the cryo-EM structure of the ligand-bound ectodomain in the full-length human IGF-1R. We reconstructed the IGF-1R/insulin complex at 4.7 Å and the IGF-1R/IGF-1 complex at 7.7 Å. Our structures reveal that only one insulin or one IGF-1 molecule binds to and activates the full-length human IGF-1R receptor. | ||||||||||||
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 | 分子: MolmilJmol/JSmol |
-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 6jk8.cif.gz | 334.4 KB | 表示 | PDBx/mmCIF形式 |
---|---|---|---|---|
PDB形式 | pdb6jk8.ent.gz | 259.6 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 6jk8.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
文書・要旨 | 6jk8_validation.pdf.gz | 1.1 MB | 表示 | wwPDB検証レポート |
---|---|---|---|---|
文書・詳細版 | 6jk8_full_validation.pdf.gz | 1.1 MB | 表示 | |
XML形式データ | 6jk8_validation.xml.gz | 59.8 KB | 表示 | |
CIF形式データ | 6jk8_validation.cif.gz | 88 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/jk/6jk8 ftp://data.pdbj.org/pub/pdb/validation_reports/jk/6jk8 | HTTPS FTP |
-関連構造データ
-リンク
-集合体
登録構造単位 |
|
---|---|
1 |
|
-要素
#1: タンパク質 | 分子量: 154964.469 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: IGF1R / 細胞株 (発現宿主): HEK293T / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: P08069, receptor protein-tyrosine kinase #2: タンパク質 | 分子量: 11989.862 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: INS / 細胞株 (発現宿主): HEK293T / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: P01308 #3: 多糖 | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose #4: 多糖 | alpha-D-mannopyranose-(1-4)-alpha-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1- ...alpha-D-mannopyranose-(1-4)-alpha-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose | #5: 糖 | ChemComp-NAG / 研究の焦点であるリガンドがあるか | N | 配列の詳細 | Authors state that the part of the chain A (698A-736A) and the part of the chain B (698B-736B) are ...Authors state that the part of the chain A (698A-736A) and the part of the chain B (698B-736B) are not able to assign which one belongs which one, due to the broken ends. | |
---|
-実験情報
-実験
実験 | 手法: 電子顕微鏡法 |
---|---|
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: complex of full-length human type 1 insulin-like growth factor receptor with insulin タイプ: COMPLEX / Entity ID: #2 / 由来: RECOMBINANT |
---|---|
分子量 | 値: 0.31 MDa / 実験値: YES |
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: HEK293T |
緩衝液 | pH: 7.4 / 詳細: PBS with detergent |
試料 | 濃度: 2 mg/ml / 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES 詳細: human type 1 insulin-like growth factor receptor saturated with human insulin |
試料支持 | グリッドの材料: GOLD / 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 IV / 凍結剤: ETHANE / 湿度: 100 % / 凍結前の試料温度: 278 K |
-電子顕微鏡撮影
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
---|---|
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 FIELD / 倍率(公称値): 105000 X / 倍率(補正後): 36496 X / Cs: 2.7 mm |
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 QUANTUM (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 | ||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
EMソフトウェア |
| ||||||||||||||||||||||||
CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3次元再構成 | 解像度: 5 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 301139 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
精密化 | 最高解像度: 4.7 Å |