Sandbox Reserved 427
From Proteopedia
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===Binding Interactions=== | ===Binding Interactions=== | ||
| + | 2dtg | ||
| + | transmembrane receptor activated in the presence of insulin, a member of the tyrosine kinase class of receptor proteins | ||
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| + | Tyrosine Kinases in General | ||
| + | Class of receptor proteins that add a phosphate group to a tyrosine on their specific substrate. | ||
| + | |||
| + | |||
| + | Interactions with insulin (IRS-1) and subsequent binding/phosphorylation. This leads to an increase in the glucose transporter (Glut-4) which has a high affinity for glucose molecules. This occurs mainly in muscle and adipose tissues where glucose uptake is most needed. This increase in Glut-4 causes an increase in glucose uptake from blood. Simply stated, 2dtg is activated by insulin which signals for an increase in Glut-4. Glut-4 finds its way to the cell surface where it can perform its function (transport glucose into the cell). | ||
| + | |||
| + | Green scene of the active site of 2dtg (tyrosine kinase) | ||
===Additional Features=== | ===Additional Features=== | ||
Revision as of 17:13, 4 March 2012
| 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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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
2dtg transmembrane receptor activated in the presence of insulin, a member of the tyrosine kinase class of receptor proteins
Tyrosine Kinases in General Class of receptor proteins that add a phosphate group to a tyrosine on their specific substrate.
Interactions with insulin (IRS-1) and subsequent binding/phosphorylation. This leads to an increase in the glucose transporter (Glut-4) which has a high affinity for glucose molecules. This occurs mainly in muscle and adipose tissues where glucose uptake is most needed. This increase in Glut-4 causes an increase in glucose uptake from blood. Simply stated, 2dtg is activated by insulin which signals for an increase in Glut-4. Glut-4 finds its way to the cell surface where it can perform its function (transport glucose into the cell).
Green scene of the active site of 2dtg (tyrosine kinase)
Additional Features
Credits
Introduction - Rebecca Bishop
Overall Structure - Kathryn Liedell
Drug Binding Site - Ryan Deeney
Additional Features - Jeffrey Boerth
