- EMDB-28693: Cryo-EM structure of two IGF1 bound full-length mouse IGF1R mutan... -
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基本情報
登録情報
データベース: EMDB / ID: EMD-28693
タイトル
Cryo-EM structure of two IGF1 bound full-length mouse IGF1R mutant (four glycine residues inserted in the alpha-CT; IGF1R-P674G4): symmetric conformation
マップデータ
Cryo-EM structure of two IGF1 bound full-length mouse IGF1R mutant (four glycine residues inserted in the alpha-CT; IGF1R-P674G4): symmetric conformation
試料
複合体: Two IGF1 bound full-length mouse IGF1R mutant (four glycine residues inserted in the alpha-CT; IGF1R-P674G4): symmetric conformation
タンパク質・ペプチド: Insulin-like growth factor 1 receptor
タンパク質・ペプチド: Insulin-like growth factor I
機能・相同性
機能・相同性情報
Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R) / mitotic nuclear division / IRS-related events triggered by IGF1R / SHC-related events triggered by IGF1R / glycolate metabolic process / muscle hypertrophy / negative regulation of oocyte development / positive regulation of trophectodermal cell proliferation / insulin-like growth factor binding protein complex / insulin-like growth factor ternary complex ...Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R) / mitotic nuclear division / IRS-related events triggered by IGF1R / SHC-related events triggered by IGF1R / glycolate metabolic process / muscle hypertrophy / negative regulation of oocyte development / positive regulation of trophectodermal cell proliferation / insulin-like growth factor binding protein complex / insulin-like growth factor ternary complex / : / proteoglycan biosynthetic process / negative regulation of cholangiocyte apoptotic process / positive regulation of glycoprotein biosynthetic process / myotube cell development / Extra-nuclear estrogen signaling / skeletal muscle satellite cell maintenance involved in skeletal muscle regeneration / insulin-like growth factor receptor activity / positive regulation of steroid hormone biosynthetic process / protein kinase complex / negative regulation of neuroinflammatory response / bone mineralization involved in bone maturation / negative regulation of vascular associated smooth muscle cell apoptotic process / Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R) / positive regulation of cell growth involved in cardiac muscle cell development / protein transporter activity / IRS-related events triggered by IGF1R / insulin-like growth factor binding / exocytic vesicle / negative regulation of muscle cell apoptotic process / positive regulation of meiotic cell cycle / positive regulation of DNA metabolic process / positive regulation of developmental growth / cell activation / positive regulation of calcineurin-NFAT signaling cascade / male sex determination / prostate gland epithelium morphogenesis / exocrine pancreas development / mammary gland development / insulin receptor complex / negative regulation of hepatocyte apoptotic process / positive regulation of transcription regulatory region DNA binding / insulin-like growth factor I binding / insulin receptor activity / transcytosis / alphav-beta3 integrin-IGF-1-IGF1R complex / positive regulation of kinase activity / positive regulation of Ras protein signal transduction / positive regulation of protein-containing complex disassembly / myoblast differentiation / positive regulation of insulin-like growth factor receptor signaling pathway / myoblast proliferation / muscle organ development / negative regulation of interleukin-1 beta production / dendritic spine maintenance / cellular response to insulin-like growth factor stimulus / response to L-glutamate / insulin binding / negative regulation of MAPK cascade / adrenal gland development / establishment of cell polarity / postsynaptic modulation of chemical synaptic transmission / protein tyrosine kinase activator activity / positive regulation of cardiac muscle hypertrophy / positive regulation of activated T cell proliferation / positive regulation of smooth muscle cell migration / positive regulation of axon regeneration / amyloid-beta clearance / negative regulation of release of cytochrome c from mitochondria / positive regulation of osteoblast proliferation / positive regulation of cytokinesis / negative regulation of amyloid-beta formation / negative regulation of smooth muscle cell apoptotic process / phosphatidylinositol-mediated signaling / regulation of JNK cascade / negative regulation of tumor necrosis factor production / insulin receptor substrate binding / estrous cycle / positive regulation of glycogen biosynthetic process / G-protein alpha-subunit binding / Synthesis, secretion, and deacylation of Ghrelin / epidermis development / epithelial to mesenchymal transition / negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / positive regulation of DNA binding / SHC-related events triggered by IGF1R / positive regulation of osteoblast differentiation / phosphatidylinositol 3-kinase binding / peptidyl-tyrosine autophosphorylation / positive regulation of tyrosine phosphorylation of STAT protein / positive regulation of vascular associated smooth muscle cell proliferation / cellular response to transforming growth factor beta stimulus / cell surface receptor protein tyrosine kinase signaling pathway / T-tubule / positive regulation of glycolytic process / activation of protein kinase B activity / transmembrane receptor protein tyrosine kinase activity / protein serine/threonine kinase activator activity / positive regulation of mitotic nuclear division / cerebellum development 類似検索 - 分子機能
Insulin-like growth factor I / Insulin-like growth factor / Tyrosine-protein kinase, insulin-like receptor / Tyrosine-protein kinase, receptor class II, conserved site / Receptor tyrosine kinase class II signature. / Insulin family / Insulin/IGF/Relaxin family / Insulin, conserved site / Insulin family signature. / Insulin-like ...Insulin-like growth factor I / Insulin-like growth factor / Tyrosine-protein kinase, insulin-like receptor / Tyrosine-protein kinase, receptor class II, conserved site / Receptor tyrosine kinase class II signature. / Insulin family / Insulin/IGF/Relaxin family / Insulin, conserved site / Insulin family signature. / Insulin-like / Insulin / insulin-like growth factor / relaxin family. / Insulin-like superfamily / Receptor L-domain / Furin-like cysteine-rich domain / Receptor L-domain superfamily / Furin-like cysteine rich region / Receptor L domain / Furin-like repeat / Furin-like repeats / Growth factor receptor cysteine-rich domain superfamily / Fibronectin type 3 domain / Fibronectin type-III domain profile. / Fibronectin type III / Fibronectin type III superfamily / Tyrosine-protein kinase, catalytic domain / Tyrosine kinase, catalytic domain / Tyrosine protein kinases specific active-site signature. / Tyrosine-protein kinase, active site / Protein tyrosine and serine/threonine kinase / Serine-threonine/tyrosine-protein kinase, catalytic domain / Protein kinase, ATP binding site / Protein kinases ATP-binding region signature. / Immunoglobulin-like fold / Protein kinase domain profile. / Protein kinase domain / Protein kinase-like domain superfamily 類似検索 - ドメイン・相同性
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
R01GM136976
米国
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
R35GM142937
米国
引用
ジャーナル: Elife / 年: 2022 タイトル: Molecular basis for the role of disulfide-linked αCTs in the activation of insulin-like growth factor 1 receptor and insulin receptor. 著者: Jie Li / Jiayi Wu / Catherine Hall / Xiao-Chen Bai / Eunhee Choi / 要旨: The insulin receptor (IR) and insulin-like growth factor 1 receptor (IGF1R) control metabolic homeostasis and cell growth and proliferation. The IR and IGF1R form similar disulfide bonds linked ...The insulin receptor (IR) and insulin-like growth factor 1 receptor (IGF1R) control metabolic homeostasis and cell growth and proliferation. The IR and IGF1R form similar disulfide bonds linked homodimers in the apo-state; however, their ligand binding properties and the structures in the active state differ substantially. It has been proposed that the disulfide-linked C-terminal segment of α-chain (αCTs) of the IR and IGF1R control the cooperativity of ligand binding and regulate the receptor activation. Nevertheless, the molecular basis for the roles of disulfide-linked αCTs in IR and IGF1R activation are still unclear. Here, we report the cryo-EM structures of full-length mouse IGF1R/IGF1 and IR/insulin complexes with modified αCTs that have increased flexibility. Unlike the -shaped asymmetric IGF1R dimer with a single IGF1 bound, the IGF1R with the enhanced flexibility of αCTs can form a -shaped symmetric dimer with two IGF1s bound. Meanwhile, the IR with non-covalently linked αCTs predominantly adopts an asymmetric conformation with four insulins bound, which is distinct from the -shaped symmetric IR. Using cell-based experiments, we further showed that both IGF1R and IR with the modified αCTs cannot activate the downstream signaling potently. Collectively, our studies demonstrate that the certain structural rigidity of disulfide-linked αCTs is critical for optimal IR and IGF1R signaling activation.
#195 - 2016年3月 RAFタンパク質キナーゼ (RAF Protein Kinases) 類似性 (1)
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マップ
ファイル
ダウンロード / ファイル: emd_28693.map.gz / 形式: CCP4 / 大きさ: 178 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
注釈
Cryo-EM structure of two IGF1 bound full-length mouse IGF1R mutant (four glycine residues inserted in the alpha-CT; IGF1R-P674G4): symmetric conformation
ボクセルのサイズ
X=Y=Z: 0.83 Å
密度
表面レベル
登録者による: 0.006
最小 - 最大
-0.026597057 - 0.049789708
平均 (標準偏差)
5.0296665e-05 (±0.0010395781)
対称性
空間群: 1
詳細
EMDB XML:
マップ形状
Axis order
X
Y
Z
Origin
0
0
0
サイズ
360
360
360
Spacing
360
360
360
セル
A=B=C: 298.8 Å α=β=γ: 90.0 °
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添付データ
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ハーフマップ: Cryo-EM structure of two IGF1 bound full-length mouse...