- EMDB-0247: Leucine-zippered human insulin receptor ectodomain with single bo... -
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基本情報
登録情報
データベース: EMDB / ID: EMD-0247
タイトル
Leucine-zippered human insulin receptor ectodomain with single bound insulin - "upper" membrane-distal part
マップデータ
human insulin receptor ectodomain with insulin bound - "upper" membrane-distal part
試料
複合体: Leucine zippered human insulin receptor ectodomain (IR-A isoform, "deltabeta" mutant) in complex with insulin and two Fv 83-7 modules : "upper" membrane-distal part
複合体: insulin
タンパク質・ペプチド: Insulin
タンパク質・ペプチド: Insulin
複合体: Leucine zippered human insulin receptor ectodomain
タンパク質・ペプチド: Insulin receptor,General control protein GCN4
リガンド: 2-acetamido-2-deoxy-beta-D-glucopyranose
機能・相同性
機能・相同性情報
regulation of female gonad development / positive regulation of meiotic cell cycle / protein localization to nuclear periphery / FCERI mediated MAPK activation / Activation of the AP-1 family of transcription factors / positive regulation of developmental growth / response to amino acid starvation / insulin-like growth factor II binding / mediator complex binding / negative regulation of ribosomal protein gene transcription by RNA polymerase II ...regulation of female gonad development / positive regulation of meiotic cell cycle / protein localization to nuclear periphery / FCERI mediated MAPK activation / Activation of the AP-1 family of transcription factors / positive regulation of developmental growth / response to amino acid starvation / insulin-like growth factor II binding / mediator complex binding / negative regulation of ribosomal protein gene transcription by RNA polymerase II / positive regulation of cellular response to amino acid starvation / male sex determination / exocrine pancreas development / insulin receptor complex / insulin-like growth factor I binding / insulin receptor activity / nitrogen catabolite activation of transcription from RNA polymerase II promoter / Oxidative Stress Induced Senescence / 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 / positive regulation of nitric oxide mediated signal transduction / negative regulation of fatty acid metabolic process / negative regulation of feeding behavior / neuronal cell body membrane / Signaling by Insulin receptor / IRS activation / activation of protein kinase activity / Insulin processing / regulation of protein secretion / amyloid-beta clearance / positive regulation of respiratory burst / positive regulation of peptide hormone secretion / Regulation of gene expression in beta cells / TFIID-class transcription factor complex binding / negative regulation of acute inflammatory response / positive regulation of receptor internalization / alpha-beta T cell activation / regulation of embryonic development / negative regulation of respiratory burst involved in inflammatory response / transport across blood-brain barrier / 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 transcription initiation by RNA polymerase II / regulation of protein localization to plasma membrane / fatty acid homeostasis / Signal attenuation / positive regulation of RNA polymerase II transcription preinitiation complex assembly / 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 / heart morphogenesis / negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway / amino acid biosynthetic process / negative regulation of reactive oxygen species biosynthetic process / positive regulation of insulin receptor signaling pathway / nitric oxide-cGMP-mediated signaling / transport vesicle / positive regulation of protein autophosphorylation / dendrite membrane / Insulin receptor recycling / neuron projection maintenance / NPAS4 regulates expression of target genes / positive regulation of protein metabolic process / cellular response to amino acid starvation / 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 / receptor-mediated endocytosis / learning / positive regulation of nitric-oxide synthase activity / positive regulation of cytokine production / positive regulation of long-term synaptic potentiation / caveola / acute-phase response / Regulation of insulin secretion / endosome lumen / positive regulation of protein secretion / positive regulation of glucose import / negative regulation of proteolysis / positive regulation of cell differentiation / regulation of transmembrane transporter activity / insulin-like growth factor receptor binding / positive regulation of MAP kinase activity 類似検索 - 分子機能
Insulin receptor, trans-membrane domain / Insulin receptor trans-membrane segment / Tyrosine-protein kinase, insulin-like receptor / Basic region leucine zipper / Basic-leucine zipper (bZIP) domain signature. / Basic-leucine zipper (bZIP) domain profile. / basic region leucin zipper / Basic-leucine zipper domain superfamily / Basic-leucine zipper domain / Tyrosine-protein kinase, receptor class II, conserved site ...Insulin receptor, trans-membrane domain / Insulin receptor trans-membrane segment / Tyrosine-protein kinase, insulin-like receptor / Basic region leucine zipper / Basic-leucine zipper (bZIP) domain signature. / Basic-leucine zipper (bZIP) domain profile. / basic region leucin zipper / Basic-leucine zipper domain superfamily / Basic-leucine zipper domain / Tyrosine-protein kinase, receptor class II, conserved site / Receptor tyrosine kinase class II signature. / Insulin / 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 III domain / 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
Insulin / General control transcription factor GCN4 / Insulin receptor 類似検索 - 構成要素
National Health and Medical Research Council (Australia)
APP1099595
オーストラリア
National Health and Medical Research Council (Australia)
APP1128553
オーストラリア
National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Disease (NIH/NIDDK)
DK013914
米国
National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Disease (NIH/NIDDK)
UC DRTC DK020595
米国
引用
ジャーナル: Nat Commun / 年: 2018 タイトル: The signalling conformation of the insulin receptor ectodomain. 著者: Felix Weis / John G Menting / Mai B Margetts / Shu Jin Chan / Yibin Xu / Norbert Tennagels / Paulus Wohlfart / Thomas Langer / Christoph W Müller / Matthias K Dreyer / Michael C Lawrence / 要旨: Understanding the structural biology of the insulin receptor and how it signals is of key importance in the development of insulin analogs to treat diabetes. We report here a cryo-electron microscopy ...Understanding the structural biology of the insulin receptor and how it signals is of key importance in the development of insulin analogs to treat diabetes. We report here a cryo-electron microscopy structure of a single insulin bound to a physiologically relevant, high-affinity version of the receptor ectodomain, the latter generated through attachment of C-terminal leucine zipper elements to overcome the conformational flexibility associated with ectodomain truncation. The resolution of the cryo-electron microscopy maps is 3.2 Å in the insulin-binding region and 4.2 Å in the membrane-proximal region. The structure reveals how the membrane proximal domains of the receptor come together to effect signalling and how insulin's negative cooperativity of binding likely arises. Our structure further provides insight into the high affinity of certain super-mitogenic insulins. Together, these findings provide a new platform for insulin analog investigation and design.
ダウンロード / ファイル: emd_0247.map.gz / 形式: CCP4 / 大きさ: 91.1 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
注釈
human insulin receptor ectodomain with insulin bound - "upper" membrane-distal part
ボクセルのサイズ
X=Y=Z: 1.04 Å
密度
表面レベル
登録者による: 0.035 / ムービー #1: 0.035
最小 - 最大
-0.13270356 - 0.2162133
平均 (標準偏差)
0.00019532986 (±0.0033116017)
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
288
288
288
Spacing
288
288
288
セル
A=B=C: 299.52 Å α=β=γ: 90.0 °
CCP4マップ ヘッダ情報:
mode
Image stored as Reals
Å/pix. X/Y/Z
1.04
1.04
1.04
M x/y/z
288
288
288
origin x/y/z
0.000
0.000
0.000
length x/y/z
299.520
299.520
299.520
α/β/γ
90.000
90.000
90.000
start NX/NY/NZ
0
0
0
NX/NY/NZ
240
240
240
MAP C/R/S
1
2
3
start NC/NR/NS
0
0
0
NC/NR/NS
288
288
288
D min/max/mean
-0.133
0.216
0.000
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添付データ
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試料の構成要素
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全体 : Leucine zippered human insulin receptor ectodomain (IR-A isoform,...
全体
名称: Leucine zippered human insulin receptor ectodomain (IR-A isoform, "deltabeta" mutant) in complex with insulin and two Fv 83-7 modules : "upper" membrane-distal part
要素
複合体: Leucine zippered human insulin receptor ectodomain (IR-A isoform, "deltabeta" mutant) in complex with insulin and two Fv 83-7 modules : "upper" membrane-distal part
複合体: insulin
タンパク質・ペプチド: Insulin
タンパク質・ペプチド: Insulin
複合体: Leucine zippered human insulin receptor ectodomain
タンパク質・ペプチド: Insulin receptor,General control protein GCN4
リガンド: 2-acetamido-2-deoxy-beta-D-glucopyranose
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超分子 #1: Leucine zippered human insulin receptor ectodomain (IR-A isoform,...
超分子
名称: Leucine zippered human insulin receptor ectodomain (IR-A isoform, "deltabeta" mutant) in complex with insulin and two Fv 83-7 modules : "upper" membrane-distal part タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1-#3 詳細: Note: Attached to the leucine-zippered insulin receptor ectodomain are two Fv 83-7 modules. One of these is present within this map volume but it is very poorly ordered and thus left ...詳細: Note: Attached to the leucine-zippered insulin receptor ectodomain are two Fv 83-7 modules. One of these is present within this map volume but it is very poorly ordered and thus left completely unmodelled. See the manuscript for further details.