Johnson's Monday Lab Sandbox for Insulin Receptor
From Proteopedia
(Difference between revisions)
| Line 7: | Line 7: | ||
The insulin receptor binds the insulin hormone and initiates a cascade of events within the cell. The receptor resides within the [http://en.wikipedia.org/wiki/Cell_membrane plasma membrane] of insulin targeted cells. These cells are found in various organs, such as the liver, and tissues, including skeletal muscle and adipose. The insulin receptor is activated by multiple insulin molecules binding to various sites on the receptor. Once activated, the receptor serves as the gateway for the regulation of various cellular processes including glucose transport, glycogen storage, [http://en.wikipedia.org/wiki/Autophagy autophagy], [http://en.wikipedia.org/wiki/Apoptosis apoptosis], and gene expression. Additionally, problems with the insulin receptor are associated with the development of diseases such as Alzheimer's, type II diabetes, and cancer <ref name="Scapin" />. Recent structures of the insulin receptor have illustrated the large scale [http://en.wikipedia.org/wiki/Conformational_change conformational changes], initiated by insulin binding. Evaluation of the structural composition and the biochemical properties of the insulin receptor reveals details about the role of the receptor in crucial cellular processes. | The insulin receptor binds the insulin hormone and initiates a cascade of events within the cell. The receptor resides within the [http://en.wikipedia.org/wiki/Cell_membrane plasma membrane] of insulin targeted cells. These cells are found in various organs, such as the liver, and tissues, including skeletal muscle and adipose. The insulin receptor is activated by multiple insulin molecules binding to various sites on the receptor. Once activated, the receptor serves as the gateway for the regulation of various cellular processes including glucose transport, glycogen storage, [http://en.wikipedia.org/wiki/Autophagy autophagy], [http://en.wikipedia.org/wiki/Apoptosis apoptosis], and gene expression. Additionally, problems with the insulin receptor are associated with the development of diseases such as Alzheimer's, type II diabetes, and cancer <ref name="Scapin" />. Recent structures of the insulin receptor have illustrated the large scale [http://en.wikipedia.org/wiki/Conformational_change conformational changes], initiated by insulin binding. Evaluation of the structural composition and the biochemical properties of the insulin receptor reveals details about the role of the receptor in crucial cellular processes. | ||
==Insulin== | ==Insulin== | ||
| - | [[Image:Insulin.png|thumb|right|150px|Figure 1: Insulin molecule]] The <scene name='83/839263/Insulin_molecule/3'>insulin molecule</scene> is a [http://en.wikipedia.org/wiki/Hormone hormone] made of two seperate amino acid chains that is synthesized and secreted from the [http://en.wikipedia.org/wiki/Pancreatic_islets islets of Langerhans] of the pancreas in response to high concentrations of glucose in the blood. Once it is secreted, insulin moves through the bloodstream and binds to unactivated insulin receptors residing in the plasma membrane. The receptor is fully activated after multiple insulin molecules are bound | + | [[Image:Insulin.png|thumb|right|150px|Figure 1: Insulin molecule. Insulin is a helical dimer. The two chains are linked by disulfide bonds. PDB ID: 1ZNI]] The <scene name='83/839263/Insulin_molecule/3'>insulin molecule</scene> is a [http://en.wikipedia.org/wiki/Hormone hormone] made of two seperate amino acid chains that is synthesized and secreted from the [http://en.wikipedia.org/wiki/Pancreatic_islets islets of Langerhans] of the pancreas in response to high concentrations of glucose in the blood. Once it is secreted, insulin moves through the bloodstream and binds to unactivated insulin receptors residing in the plasma membrane. Binding of insulin to the insulin receptor is a complex process, which involves negative cooperativity among insulin molecules. The receptor is fully activated only after multiple insulin molecules are bound. |
==Structure== | ==Structure== | ||
| - | The insulin receptor is a [http://en.wikipedia.org/wiki/Receptor_tyrosine_kinase receptor tyrosine kinase]. It is a [http://en.wikipedia.org/wiki/Heterotetramer heterotetramer] that is constructed from two [http://en.wiktionary.org/wiki/homodimer homodimers]. Each homodimer maintains an extracellular domain, transmembrane helix, and an intracellular domain. The insulin is divided into <scene name='83/839263/Alpha_and_beta_subunit/3'>alpha and beta</scene> [http://en.wikipedia.org/wiki/Protein_subunit subunits]. The alpha subunit is characterized by two leucine-rich regions and one cysteine-rich region. The beta subunit contains three fibronectin type III domains along with the transmembrane domain and intracellular tyrosine kinase domain that could not be shown in one continous PDB structure. The alpha and beta subunits of the extracellular domains fold over one another and form a <scene name='83/839263/V_shape/3'>"V" shape</scene> when the insulin receptor is inactivated. Upon activation, the extracellular domain undergoes a conformational change and forms a <scene name='83/839263/T-shape/4'>"T" shape</scene>. | + | The insulin receptor is a [http://en.wikipedia.org/wiki/Receptor_tyrosine_kinase receptor tyrosine kinase]. It is a [http://en.wikipedia.org/wiki/Heterotetramer heterotetramer] that is constructed from two [http://en.wiktionary.org/wiki/homodimer homodimers]. Each homodimer maintains an extracellular domain, transmembrane helix, and an intracellular domain. The insulin receptor is divided into <scene name='83/839263/Alpha_and_beta_subunit/3'>alpha and beta</scene> [http://en.wikipedia.org/wiki/Protein_subunit subunits]. The alpha subunit is characterized by two leucine-rich regions and one cysteine-rich region. The beta subunit contains three fibronectin type III domains along with the transmembrane domain and intracellular tyrosine kinase domain that could not be shown in one continous PDB structure. The alpha and beta subunits of the extracellular domains fold over one another and form a <scene name='83/839263/V_shape/3'>"V" shape</scene> when the insulin receptor is inactivated. Upon activation, the extracellular domain undergoes a conformational change and forms a <scene name='83/839263/T-shape/4'>"T" shape</scene>. |
[[Image:Insulin Receptor T.png|thumb|right|250px|Figure 2: Insulin receptor in the active "T" shape conformation with four insulins bound]] | [[Image:Insulin Receptor T.png|thumb|right|250px|Figure 2: Insulin receptor in the active "T" shape conformation with four insulins bound]] | ||
An additional component to the [http://en.wikipedia.org/wiki/Ectodomain ectodomain] is the <scene name='83/839263/Alpha-ct/2'> ''alpha'' chain C-terminal helix</scene>, which is also referred to as the "''alpha''-CT" <ref name= "Uchikawa" />. Each of the dimers has an "alpha"-CT. The ''alpha''-CT is a single alpha-helix and it plays an important role in insulin binding and stabilization of the "T" shape activated conformation. The ''alpha''-CT interacts with a leucine-rich region of the alpha subunit and a fibronectin type III region of the beta subunit to form the insulin binding sites known as <scene name='83/839263/Insulin_molecules_at_site_1/1'>site 1 and site 1'</scene> <ref name="Uchikawa" />. | An additional component to the [http://en.wikipedia.org/wiki/Ectodomain ectodomain] is the <scene name='83/839263/Alpha-ct/2'> ''alpha'' chain C-terminal helix</scene>, which is also referred to as the "''alpha''-CT" <ref name= "Uchikawa" />. Each of the dimers has an "alpha"-CT. The ''alpha''-CT is a single alpha-helix and it plays an important role in insulin binding and stabilization of the "T" shape activated conformation. The ''alpha''-CT interacts with a leucine-rich region of the alpha subunit and a fibronectin type III region of the beta subunit to form the insulin binding sites known as <scene name='83/839263/Insulin_molecules_at_site_1/1'>site 1 and site 1'</scene> <ref name="Uchikawa" />. | ||
Revision as of 18:32, 19 April 2020
Insulin Receptor
| |||||||||||
