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Yorodumi- PDB-7mqo: The insulin receptor ectodomain in complex with a venom hybrid in... -
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-Basic information
Entry | Database: PDB / ID: 7mqo | ||||||
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Title | The insulin receptor ectodomain in complex with a venom hybrid insulin analog - "head" region | ||||||
Components |
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Keywords | HORMONE / TOXIN / insulin / receptor / venom / cone snail | ||||||
Function / homology | Function and homology information regulation of female gonad development / positive regulation of meiotic cell cycle / positive regulation of developmental growth / insulin-like growth factor II binding / 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 ...regulation of female gonad development / positive regulation of meiotic cell cycle / positive regulation of developmental growth / insulin-like growth factor II binding / 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 / 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 / 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 / regulation of protein localization to plasma membrane / 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 / 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 / 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 / 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 / wound healing / insulin receptor binding / regulation of synaptic plasticity / negative regulation of protein catabolic process / hormone activity / receptor internalization / receptor protein-tyrosine kinase / memory / cognition / cellular response to growth factor stimulus / positive regulation of neuron projection development / positive regulation of protein localization to nucleus / Golgi lumen / peptidyl-tyrosine phosphorylation Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.4 Å | ||||||
Authors | Blakely, A.D. / Xiong, X. / Kim, J.H. / Menting, J. / Schafer, I.B. / Schubert, H.L. / Agrawal, R. / Gutmann, T. / Delaine, C. / Zhang, Y. ...Blakely, A.D. / Xiong, X. / Kim, J.H. / Menting, J. / Schafer, I.B. / Schubert, H.L. / Agrawal, R. / Gutmann, T. / Delaine, C. / Zhang, Y. / Artik, G.O. / Merriman, A. / Eckert, D. / Lawrence, M.C. / Coskun, U. / Fisher, S.J. / Forbes, B.E. / Safavi-Hemami, H. / Hill, C.P. / Chou, D.H.C. | ||||||
Funding support | 1items
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Citation | Journal: Nat Chem Biol / Year: 2022 Title: Symmetric and asymmetric receptor conformation continuum induced by a new insulin. Authors: Xiaochun Xiong / Alan Blakely / Jin Hwan Kim / John G Menting / Ingmar B Schäfer / Heidi L Schubert / Rahul Agrawal / Theresia Gutmann / Carlie Delaine / Yi Wolf Zhang / Gizem Olay Artik / ...Authors: Xiaochun Xiong / Alan Blakely / Jin Hwan Kim / John G Menting / Ingmar B Schäfer / Heidi L Schubert / Rahul Agrawal / Theresia Gutmann / Carlie Delaine / Yi Wolf Zhang / Gizem Olay Artik / Allanah Merriman / Debbie Eckert / Michael C Lawrence / Ünal Coskun / Simon J Fisher / Briony E Forbes / Helena Safavi-Hemami / Christopher P Hill / Danny Hung-Chieh Chou / Abstract: Cone snail venoms contain a wide variety of bioactive peptides, including insulin-like molecules with distinct structural features, binding modes and biochemical properties. Here, we report an active ...Cone snail venoms contain a wide variety of bioactive peptides, including insulin-like molecules with distinct structural features, binding modes and biochemical properties. Here, we report an active humanized cone snail venom insulin with an elongated A chain and a truncated B chain, and use cryo-electron microscopy (cryo-EM) and protein engineering to elucidate its interactions with the human insulin receptor (IR) ectodomain. We reveal how an extended A chain can compensate for deletion of B-chain residues, which are essential for activity of human insulin but also compromise therapeutic utility by delaying dissolution from the site of subcutaneous injection. This finding suggests approaches to developing improved therapeutic insulins. Curiously, the receptor displays a continuum of conformations from the symmetric state to a highly asymmetric low-abundance structure that displays coordination of a single humanized venom insulin using elements from both of the previously characterized site 1 and site 2 interactions. | ||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 7mqo.cif.gz | 251 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7mqo.ent.gz | 199 KB | Display | PDB format |
PDBx/mmJSON format | 7mqo.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7mqo_validation.pdf.gz | 1.2 MB | Display | wwPDB validaton report |
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Full document | 7mqo_full_validation.pdf.gz | 1.2 MB | Display | |
Data in XML | 7mqo_validation.xml.gz | 52.3 KB | Display | |
Data in CIF | 7mqo_validation.cif.gz | 76.1 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/mq/7mqo ftp://data.pdbj.org/pub/pdb/validation_reports/mq/7mqo | HTTPS FTP |
-Related structure data
Related structure data | 23949MC 7mqrC 7mqsC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | |
EM raw data | EMPIAR-10736 (Title: Cryo-EM of the human insulin receptor ectodomain in complex with an insulin analog with truncated B chain and enlongated A chain Data size: 11.7 TB Data #1: Unaligned multi-frame micrographs (40 e-/A2 dose) [micrographs - multiframe] Data #2: unaligned micrographs (60 e-/A2 dose) [micrographs - multiframe]) |
-Links
-Assembly
Deposited unit |
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Noncrystallographic symmetry (NCS) | NCS domain:
NCS domain segments:
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