Sandbox Reserved 1627: Difference between revisions

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====Alpha Subunits====

[[Image:Harrison Image2.png|thumb|right|260px|Figure 1: Insulin receptor apo receptor. Site L1' is colored a dark green, CR' is orange, L2' is bright blue, L2 is yellow, CR is red, L1 is dark blue, FnIII-1 is brown, and FnIII-2 is light pink. Insulin is shown bound and is colored dark pink. [http://www.rcsb.org/structure/6CE7 PDB 6CE7]]]

The alpha subunits make up the extracellular domain ([http://en.wikipedia.org/wiki/Ectodomain ectodomain]) of the insulin receptor and are the sites of insulin binding. The alpha subunit is comprised of two Leucine rich domains (L1 & L2), a Cysteine rich domain (CR), and a <scene name='83/832953/Alpha_c_helix/6'>C-Terminal alpha helix</scene>(Figure 1). <ref name="Scapin"> PMID 29512653 </ref> The CT-alpha helix is unique in its position that allows it to reach across the receptor and interact with the insulin at the binding site on the opposing side of the receptor. The alpha subunits are held together by a [http://en.wikipedia.org/wiki/Disulfide disulfide bond] between <scene name='83/832953/Cysteine_bond/2'>cysteine residues</scene> at the CYS524 position on each alpha subunit. The disulfide bonds are important to the overall stabilization of the molecule ~~has~~ it binds to insulin. Two types of insulin binding sites are present in the alpha subunits, <scene name='83/832953/Sites_1_and_1_prime_location/17'>sites 1 and 1'</scene> and <scene name='83/832953/Sites_2_and_2_prime_location/13'>sites 2 and 2'</scene> (Figure 2). The sites are in pairs because of the heterodimeric nature of the receptor. Due to structural differences, as well as greater surface area and accessibility, binding sites 1 and 1' have much higher affinity than that of sites 2 and 2'. Insulin can also bind at sites 2 and 2', but the location on the back of the beta sheet of the FnIII-1 domain and lack of surface area decreases the likelihood of their binding site becoming occupied as quickly. <ref name="Uchikawa"> DOI 10.7554/eLife.48630 </ref> [http://en.wikipedia.org/wiki/Transmission_electron_cryomicroscopy Cryo-EM] has imaged insulin bound structures that displayed a T-shape conformation in the alpha subunits, which make up the receptors extracellular domain region.<ref name="Uchikawa" />

The alpha subunits make up the extracellular domain ([http://en.wikipedia.org/wiki/Ectodomain ectodomain]) of the insulin receptor and are the sites of insulin binding. The alpha subunit is comprised of two Leucine rich domains (L1 & L2), a Cysteine rich domain (CR), and a <scene name='83/832953/Alpha_c_helix/6'>C-Terminal alpha helix</scene> (Figure 1). <ref name="Scapin"> PMID 29512653 </ref> The CT-alpha helix is unique in its position that allows it to reach across the receptor and interact with the insulin at the binding site on the opposing side of the receptor. The alpha subunits are held together by a [http://en.wikipedia.org/wiki/Disulfide disulfide bond] between <scene name='83/832953/Cysteine_bond/2'>cysteine residues</scene> at the CYS524 position on each alpha subunit. The disulfide bonds are important to the overall stabilization of the molecule as it binds to insulin. Two types of insulin binding sites are present in the alpha subunits, <scene name='83/832953/Sites_1_and_1_prime_location/17'>sites 1 and 1'</scene> and <scene name='83/832953/Sites_2_and_2_prime_location/13'>sites 2 and 2'</scene> (Figure 2). The sites are in pairs because of the heterodimeric nature of the receptor. Due to structural differences, as well as greater surface area and accessibility, binding sites 1 and 1' have much higher affinity than that of sites 2 and 2'. Insulin can also bind at sites 2 and 2', but the location on the back of the beta sheet of the FnIII-1 domain and lack of surface area decreases the likelihood of their binding site becoming occupied as quickly. <ref name="Uchikawa"> DOI 10.7554/eLife.48630 </ref> [http://en.wikipedia.org/wiki/Transmission_electron_cryomicroscopy Cryo-EM] has imaged insulin bound structures that displayed a T-shape conformation in the alpha subunits, which make up the receptors extracellular domain region.<ref name="Uchikawa" />

[[Image:4 sites highlighted - Harrison.png|thumb|right|260px|Figure 2: The four binding sites of insulin. Sites 1 and 1' are colored green, sites 2 and 2' are colored red. [http://www.rcsb.org/structure/6SOF PDB 6SOF]]]

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@@ Line 11: / Line 11: @@
 ====Alpha Subunits====
 [[Image:Harrison Image2.png|thumb|right|260px|Figure 1: Insulin receptor apo receptor. Site L1' is colored a dark green, CR' is orange, L2' is bright blue, L2 is yellow, CR is red, L1 is dark blue, FnIII-1 is brown, and FnIII-2 is light pink. Insulin is shown bound and is colored dark pink. [http://www.rcsb.org/structure/6CE7 PDB 6CE7]]]
-The alpha subunits make up the extracellular domain ([http://en.wikipedia.org/wiki/Ectodomain ectodomain]) of the insulin receptor and are the sites of insulin binding. The alpha subunit is comprised of two Leucine rich domains (L1 & L2), a Cysteine rich domain (CR), and a <scene name='83/832953/Alpha_c_helix/6'>C-Terminal alpha helix</scene>(Figure 1). <ref name="Scapin"> PMID 29512653 </ref> The CT-alpha helix is unique in its position that allows it to reach across the receptor and interact with the insulin at the binding site on the opposing side of the receptor. The alpha subunits are held together by a [http://en.wikipedia.org/wiki/Disulfide disulfide bond] between <scene name='83/832953/Cysteine_bond/2'>cysteine residues</scene> at the CYS524 position on each alpha subunit. The disulfide bonds are important to the overall stabilization of the molecule has it binds to insulin. Two types of insulin binding sites are present in the alpha subunits, <scene name='83/832953/Sites_1_and_1_prime_location/17'>sites 1 and 1'</scene> and <scene name='83/832953/Sites_2_and_2_prime_location/13'>sites 2 and 2'</scene> (Figure 2). The sites are in pairs because of the heterodimeric nature of the receptor. Due to structural differences, as well as greater surface area and accessibility, binding sites 1 and 1' have much higher affinity than that of sites 2 and 2'. Insulin can also bind at sites 2 and 2', but the location on the back of the beta sheet of the FnIII-1 domain and lack of surface area decreases the likelihood of their binding site becoming occupied as quickly. <ref name="Uchikawa"> DOI 10.7554/eLife.48630 </ref> [http://en.wikipedia.org/wiki/Transmission_electron_cryomicroscopy Cryo-EM] has imaged insulin bound structures that displayed a T-shape conformation in the alpha subunits, which make up the receptors extracellular domain region.<ref name="Uchikawa" />
+The alpha subunits make up the extracellular domain ([http://en.wikipedia.org/wiki/Ectodomain ectodomain]) of the insulin receptor and are the sites of insulin binding. The alpha subunit is comprised of two Leucine rich domains (L1 & L2), a Cysteine rich domain (CR), and a <scene name='83/832953/Alpha_c_helix/6'>C-Terminal alpha helix</scene> (Figure 1). <ref name="Scapin"> PMID 29512653 </ref> The CT-alpha helix is unique in its position that allows it to reach across the receptor and interact with the insulin at the binding site on the opposing side of the receptor. The alpha subunits are held together by a [http://en.wikipedia.org/wiki/Disulfide disulfide bond] between <scene name='83/832953/Cysteine_bond/2'>cysteine residues</scene> at the CYS524 position on each alpha subunit. The disulfide bonds are important to the overall stabilization of the molecule as it binds to insulin. Two types of insulin binding sites are present in the alpha subunits, <scene name='83/832953/Sites_1_and_1_prime_location/17'>sites 1 and 1'</scene> and <scene name='83/832953/Sites_2_and_2_prime_location/13'>sites 2 and 2'</scene> (Figure 2). The sites are in pairs because of the heterodimeric nature of the receptor. Due to structural differences, as well as greater surface area and accessibility, binding sites 1 and 1' have much higher affinity than that of sites 2 and 2'. Insulin can also bind at sites 2 and 2', but the location on the back of the beta sheet of the FnIII-1 domain and lack of surface area decreases the likelihood of their binding site becoming occupied as quickly. <ref name="Uchikawa"> DOI 10.7554/eLife.48630 </ref> [http://en.wikipedia.org/wiki/Transmission_electron_cryomicroscopy Cryo-EM] has imaged insulin bound structures that displayed a T-shape conformation in the alpha subunits, which make up the receptors extracellular domain region.<ref name="Uchikawa" />
 [[Image:4 sites highlighted - Harrison.png|thumb|right|260px|Figure 2: The four binding sites of insulin. Sites 1 and 1' are colored green, sites 2 and 2' are colored red.  [http://www.rcsb.org/structure/6SOF PDB 6SOF]]]