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基本情報
登録情報 | データベース: PDB / ID: 8cls | |||||||||
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タイトル | Drosophila melanogaster insulin receptor ectodomain in complex with DILP5 | |||||||||
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![]() | SIGNALING PROTEIN / DILP5 hormone / Drosophila insulin-like signalling receptor / disulfide linked ectodomain | |||||||||
機能・相同性 | ![]() primary spermatocyte growth / negative regulation of peptide hormone secretion / Extra-nuclear estrogen signaling / negative regulation of entry into reproductive diapause / Insulin signaling pathway / Insulin receptor recycling / female mating behavior / response to anoxia / embryonic development via the syncytial blastoderm / male germ-line stem cell asymmetric division ...primary spermatocyte growth / negative regulation of peptide hormone secretion / Extra-nuclear estrogen signaling / negative regulation of entry into reproductive diapause / Insulin signaling pathway / Insulin receptor recycling / female mating behavior / response to anoxia / embryonic development via the syncytial blastoderm / male germ-line stem cell asymmetric division / female germ-line stem cell population maintenance / germ-band shortening / histone H2AXY142 kinase activity / carbohydrate homeostasis / germ-line stem-cell niche homeostasis / imaginal disc growth / negative regulation of circadian sleep/wake cycle, sleep / open tracheal system development / positive regulation of neuron remodeling / germ-line stem cell division / follicle cell of egg chamber development / lymph gland development / positive regulation of border follicle cell migration / female germ-line stem cell asymmetric division / positive regulation of fat cell proliferation / intestinal stem cell homeostasis / growth cone membrane / positive regulation of organ growth / histone H3Y41 kinase activity / positive regulation of lipid storage / insulin receptor complex / regulation of organ growth / positive regulation of multicellular organism growth / sleep / triglyceride homeostasis / embryo development ending in birth or egg hatching / insulin binding / positive regulation of wound healing / negative regulation of macroautophagy / negative regulation of feeding behavior / positive regulation of neuroblast proliferation / female gonad development / lipid homeostasis / insulin receptor substrate binding / regulation of multicellular organism growth / positive regulation of cell size / developmental growth / phosphatidylinositol 3-kinase binding / axon guidance / cell surface receptor protein tyrosine kinase signaling pathway / cholesterol homeostasis / cellular response to starvation / determination of adult lifespan / locomotory behavior / insulin receptor binding / response to cocaine / placental growth factor receptor activity / insulin receptor activity / hepatocyte growth factor receptor activity / macrophage colony-stimulating factor receptor activity / platelet-derived growth factor alpha-receptor activity / platelet-derived growth factor beta-receptor activity / stem cell factor receptor activity / boss receptor activity / protein tyrosine kinase collagen receptor activity / brain-derived neurotrophic factor receptor activity / transmembrane-ephrin receptor activity / GPI-linked ephrin receptor activity / epidermal growth factor receptor activity / fibroblast growth factor receptor activity / insulin-like growth factor receptor activity / receptor protein-tyrosine kinase / hormone activity / multicellular organism growth / SH3 domain binding / circadian rhythm / insulin receptor signaling pathway / glucose homeostasis / nervous system development / regulation of cell population proliferation / positive regulation of cell growth / protein autophosphorylation / protein tyrosine kinase activity / response to oxidative stress / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / positive regulation of MAPK cascade / protein phosphorylation / receptor ligand activity / axon / positive regulation of cell population proliferation / extracellular space / extracellular region / ATP binding / metal ion binding / identical protein binding / plasma membrane 類似検索 - 分子機能 | |||||||||
生物種 | ![]() ![]() | |||||||||
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 | |||||||||
![]() | Viola, C.M. / Brzozowski, A.M. / Shafi, T. | |||||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Structural conservation of insulin/IGF signalling axis at the insulin receptors level in Drosophila and humans. 著者: Cristina M Viola / Orsolya Frittmann / Huw T Jenkins / Talha Shafi / Pierre De Meyts / Andrzej M Brzozowski / ![]() ![]() ![]() ![]() 要旨: The insulin-related hormones regulate key life processes in Metazoa, from metabolism to growth, lifespan and aging, through an evolutionarily conserved insulin signalling axis (IIS). In humans the ...The insulin-related hormones regulate key life processes in Metazoa, from metabolism to growth, lifespan and aging, through an evolutionarily conserved insulin signalling axis (IIS). In humans the IIS axis is controlled by insulin, two insulin-like growth factors, two isoforms of the insulin receptor (hIR-A and -B), and its homologous IGF-1R. In Drosophila, this signalling engages seven insulin-like hormones (DILP1-7) and a single receptor (dmIR). This report describes the cryoEM structure of the dmIR ectodomain:DILP5 complex, revealing high structural homology between dmIR and hIR. The excess of DILP5 yields dmIR complex in an asymmetric 'T' conformation, similar to that observed in some complexes of human IRs. However, dmIR binds three DILP5 molecules in a distinct arrangement, showing also dmIR-specific features. This work adds structural support to evolutionary conservation of the IIS axis at the IR level, and also underpins a better understanding of an important model organism. | |||||||||
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構造の表示
構造ビューア | 分子: ![]() ![]() |
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PDBx/mmCIF形式 | ![]() | 601.5 KB | 表示 | ![]() |
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-検証レポート
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
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-関連構造データ
関連構造データ | ![]() 16718MC M: このデータのモデリングに利用したマップデータ C: 同じ文献を引用 ( |
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類似構造データ | 類似検索 - 機能・相同性 ![]() |
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リンク
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集合体
登録構造単位 | ![]()
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要素
#1: タンパク質 | 分子量: 120074.641 Da / 分子数: 2 / 由来タイプ: 組換発現 由来: (組換発現) ![]() ![]() 遺伝子: InR, dinr, Dir-a, Inr-a, CG18402 / 細胞株 (発現宿主): Sf9 発現宿主: ![]() ![]() 参照: UniProt: P09208, receptor protein-tyrosine kinase #2: タンパク質・ペプチド | 分子量: 2795.097 Da / 分子数: 3 / 由来タイプ: 合成 由来: (合成) ![]() ![]() 参照: UniProt: Q7KUD5 #3: タンパク質・ペプチド | 分子量: 3018.603 Da / 分子数: 3 / 由来タイプ: 合成 由来: (合成) ![]() ![]() 参照: UniProt: Q7KUD5 Has protein modification | Y | |
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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 |
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試料調製
構成要素 |
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分子量 |
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由来(天然) |
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由来(組換発現) |
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緩衝液 | pH: 7.4 | ||||||||||||||||||
試料 | 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES | ||||||||||||||||||
試料支持 | グリッドのタイプ: Quantifoil R1.2/1.3 | ||||||||||||||||||
急速凍結 | 凍結剤: ETHANE |
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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: ![]() |
電子レンズ | モード: BRIGHT FIELD / 最大 デフォーカス(公称値): 4000 nm / 最小 デフォーカス(公称値): 500 nm |
撮影 | 電子線照射量: 0.829 e/Å2 / フィルム・検出器のモデル: GATAN K3 (6k x 4k) |
画像スキャン | 横: 5760 / 縦: 4092 |
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解析
EMソフトウェア | 名称: PHENIX / バージョン: 1.20.1_4487: / カテゴリ: モデル精密化 | ||||||||||||||||||||||||
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CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
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: 129444 / 対称性のタイプ: POINT | ||||||||||||||||||||||||
原子モデル構築 | プロトコル: RIGID BODY FIT / 空間: REAL 詳細: Local fitting of Alphafold predicted domains was done using ChimeraX | ||||||||||||||||||||||||
精密化 | 解像度: 4→172.25 Å / Cor.coef. Fo:Fc: 0.983 / SU B: 23.071 / SU ML: 0.31 / ESU R: 0.48 立体化学のターゲット値: MAXIMUM LIKELIHOOD WITH PHASES 詳細: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
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溶媒の処理 | 溶媒モデル: PARAMETERS FOR MASK CACLULATION | ||||||||||||||||||||||||
原子変位パラメータ | Biso mean: 217.696 Å2 | ||||||||||||||||||||||||
精密化ステップ | サイクル: 1 / 合計: 14494 | ||||||||||||||||||||||||
拘束条件 |
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LS精密化 シェル | 解像度: 4→4.104 Å / Total num. of bins used: 20
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