+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 7stk | ||||||
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タイトル | Full-length insulin receptor bound with unsaturated insulin WT (2 insulins bound) asymmetric conformation (Conformation 2) | ||||||
要素 |
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キーワード | SIGNALING PROTEIN / insulin receptor (インスリン受容体) / site 1 binding deficient mutant insulin | ||||||
機能・相同性 | 機能・相同性情報 Signaling by Insulin receptor / Insulin receptor recycling / 卵黄 / IRS activation / Insulin receptor signalling cascade / Signal attenuation / 3-phosphoinositide-dependent protein kinase binding / positive regulation of glycoprotein biosynthetic process / lipoic acid binding / regulation of hydrogen peroxide metabolic process ...Signaling by Insulin receptor / Insulin receptor recycling / 卵黄 / IRS activation / Insulin receptor signalling cascade / Signal attenuation / 3-phosphoinositide-dependent protein kinase binding / positive regulation of glycoprotein biosynthetic process / lipoic acid binding / regulation of hydrogen peroxide metabolic process / regulation of female gonad development / positive regulation of meiotic cell cycle / PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling / positive regulation of developmental growth / insulin-like growth factor II binding / nuclear lumen / 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 / PTB domain binding / negative regulation of NAD(P)H oxidase activity / negative regulation of glycogen catabolic process / regulation of cellular amino acid metabolic process / adrenal gland development / negative regulation of fatty acid metabolic process / neuronal cell body membrane / negative regulation of feeding behavior / Signaling by Insulin receptor / nitric oxide-cGMP-mediated signaling / IRS activation / Insulin processing / regulation of protein secretion / amyloid-beta clearance / positive regulation of peptide hormone secretion / positive regulation of respiratory burst / Regulation of gene expression in beta cells / negative regulation of acute inflammatory response / regulation of embryonic development / positive regulation of receptor internalization / alpha-beta T cell activation / negative regulation of respiratory burst involved in inflammatory response / insulin receptor substrate binding / positive regulation of dendritic spine maintenance / positive regulation of glycogen biosynthetic process / Synthesis, secretion, and deacylation of Ghrelin / epidermis development / negative regulation of protein secretion / positive regulation of nitric oxide mediated signal transduction / fatty acid homeostasis / regulation of protein localization to plasma membrane / Signal attenuation / FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes / response to tumor necrosis factor / negative regulation of lipid catabolic process / negative regulation of gluconeogenesis / phosphatidylinositol 3-kinase binding / COPI-mediated anterograde transport / positive regulation of lipid biosynthetic process / heart morphogenesis / negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway / negative regulation of reactive oxygen species biosynthetic process / positive regulation of insulin receptor signaling pathway / positive regulation of phosphorylation / 小胞 / positive regulation of protein autophosphorylation / dendrite membrane / Insulin receptor recycling / insulin-like growth factor receptor binding / neuron projection maintenance / NPAS4 regulates expression of target genes / positive regulation of protein metabolic process / positive regulation of brown fat cell differentiation / endoplasmic reticulum-Golgi intermediate compartment membrane / positive regulation of glycolytic process / activation of protein kinase B activity / positive regulation of mitotic nuclear division / receptor-mediated endocytosis / Insulin receptor signalling cascade / response to nutrient levels / negative regulation of protein phosphorylation / positive regulation of cytokine production / positive regulation of long-term synaptic potentiation / Regulation of insulin secretion / カベオラ / acute-phase response / endosome lumen / positive regulation of protein secretion / positive regulation of glucose import / positive regulation of nitric-oxide synthase activity / positive regulation of cell differentiation / negative regulation of proteolysis / regulation of transmembrane transporter activity / animal organ morphogenesis / wound healing 類似検索 - 分子機能 | ||||||
生物種 | Mus musculus (ハツカネズミ) 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: 4 Å | ||||||
データ登録者 | Bai, X.C. / Choi, E. | ||||||
資金援助 | 米国, 1件
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引用 | ジャーナル: Nat Struct Mol Biol / 年: 2022 タイトル: Synergistic activation of the insulin receptor via two distinct sites. 著者: Jie Li / Junhee Park / John P Mayer / Kristofor J Webb / Emiko Uchikawa / Jiayi Wu / Shun Liu / Xuewu Zhang / Michael H B Stowell / Eunhee Choi / Xiao-Chen Bai / 要旨: Insulin receptor (IR) signaling controls multiple facets of animal physiology. Maximally four insulins bind to IR at two distinct sites, termed site-1 and site-2. However, the precise functional ...Insulin receptor (IR) signaling controls multiple facets of animal physiology. Maximally four insulins bind to IR at two distinct sites, termed site-1 and site-2. However, the precise functional roles of each binding event during IR activation remain unresolved. Here, we showed that IR incompletely saturated with insulin predominantly forms an asymmetric conformation and exhibits partial activation. IR with one insulin bound adopts a Γ-shaped conformation. IR with two insulins bound assumes a Ƭ-shaped conformation. One insulin binds at site-1 and another simultaneously contacts both site-1 and site-2 in the Ƭ-shaped IR dimer. We further show that concurrent binding of four insulins to sites-1 and -2 prevents the formation of asymmetric IR and promotes the T-shaped symmetric, fully active state. Collectively, our results demonstrate how the synergistic binding of multiple insulins promotes optimal IR activation. | ||||||
履歴 |
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-構造の表示
構造ビューア | 分子: MolmilJmol/JSmol |
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-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 7stk.cif.gz | 363.7 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb7stk.ent.gz | 290.4 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 7stk.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
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/st/7stk ftp://data.pdbj.org/pub/pdb/validation_reports/st/7stk | HTTPS FTP |
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-関連構造データ
関連構造データ | 25431MC 7sl1C 7sl2C 7sl3C 7sl4C 7sl6C 7sl7C 7sthC 7stiC 7stjC C: 同じ文献を引用 (文献) M: このデータのモデリングに利用したマップデータ |
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類似構造データ | 類似検索 - 機能・相同性F&H 検索 |
-リンク
-集合体
登録構造単位 |
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1 |
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-要素
#1: タンパク質 | 分子量: 155790.516 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) Mus musculus (ハツカネズミ) / 遺伝子: Insr / 発現宿主: Homo sapiens (ヒト) 参照: UniProt: P15208, 受容体型チロシンキナーゼ #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 / 発現宿主: Homo sapiens (ヒト) / 参照: UniProt: P01308 |
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-実験情報
-実験
実験 | 手法: 電子顕微鏡法 |
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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: Full-length insulin receptor bound with unsaturated insulin WT (2 insulins bound) asymmetric conformation (Conformation 2) タイプ: COMPLEX / Entity ID: all / 由来: RECOMBINANT |
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分子量 | 実験値: NO |
由来(天然) | 生物種: Mus musculus (ハツカネズミ) |
由来(組換発現) | 生物種: Homo sapiens (ヒト) |
緩衝液 | pH: 8 |
試料 | 濃度: 6 mg/ml / 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES |
急速凍結 | 装置: FEI VITROBOT MARK IV / 凍結剤: ETHANE / 湿度: 100 % |
-電子顕微鏡撮影
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
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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 FIELDBright-field microscopy / 最大 デフォーカス(公称値): 2600 nm / 最小 デフォーカス(公称値): 1600 nm |
撮影 | 電子線照射量: 60 e/Å2 フィルム・検出器のモデル: GATAN K3 BIOQUANTUM (6k x 4k) |
-解析
EMソフトウェア |
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CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||||||||||
粒子像の選択 | 選択した粒子像数: 2030596 | ||||||||||||||||||||||||||||||||||||||||
3次元再構成 | 解像度: 4 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 46052 / 対称性のタイプ: POINT |