Sandbox Reserved 427

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This Sandbox is Reserved from January 19, 2016, through August 31, 2016 for use for Proteopedia Team Projects by the class Chemistry 423 Biochemistry for Chemists taught by Lynmarie K Thompson at University of Massachusetts Amherst, USA. This reservation includes Sandbox Reserved 425 through Sandbox Reserved 439.


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==YourMacromolecule==

Contents

Introduction

Insulin receptor ABOUT -tyrosine kinase (ligand-activated receptor kinase) 

  -expressed at cell surface as homodimers composed of alpha/beta monomers
     -disulfide-linked ectodomain dimer - folded over conformation places ligands in correct relative positions (green scene)
  -mediate activity by addition of phophate to tyrosines on specific proteins in cell

-found in organisms from cnidarians and insects to humans 

  -in humans essential for maintaining glucose levels
  -also has role in growth and development (insulin growth factor II)
     -signal through IGF2 to mediate embryonic growth (Kitamura et al)

FUNCTION -insulin receptor substrate 1 (IRS-1) binding leads to increase in high affinity glucose transporter (Glut4) molecules on the other membrane of cell (muscles, adipose) 

  -leads to increased glu uptake (Glut4 mediates transport of glu into cell)

DISEASE -decreased insulin resceptor signalling (aka insulin insensitivity)leads to diabetes mellitus type 2 

   - cells unable to take up glu => hyperglycemia (increased circulating glucose)
   -aka non-insulin-dependent or adult onset diabetes
      -beleived to be caused by obesity and genetic predisposition
      -managed with dietary and lifestyle modifications

-mutations in both copies of the insulin receptor gene causes Donohue syndrome (leprechaunism) 

   -autosomal recessive; results in totally non-functional insulin receptor
   -results in distorted facial features, growth redardation and often death within a year

Overall Structure

-Ectodomain is dimer of 2 identical monomers (dimer green scene)

-Monomers composed of 6 domains (monomer green scene)

-Leucine-rich repeat domain (L1), secondary structures (green scene)

-Cystine-rich region (CR), secondary structures (green scene)

-Leucine-rich repeat domain (L2), secondary structures (green scene)

-Fibronectin Type III domain 1 (FnIII-1), secondary structures (green scene)

-Fibronectin Type III domain 2 (FnIII-2), secondary structures, insert domain (green scene)

-Fibronectin Type III domain 3 (FnIII-3), secondary structures (green scene)

Binding Interactions

Additional Features

Credits

Introduction - Rebecca Bishop

Overall Structure - Kathryn Liedell

Drug Binding Site - Ryan Deeney

Additional Features - Jeffrey Boerth

References

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