Sandbox Reserved 1703: Difference between revisions
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mGlu2 is a [https://en.wikipedia.org/wiki/Protein_dimer homodimer]. Dimerization of mGlu2 is required to relay glutamate binding from the ECD to its transmembrane domain TMD. The homodimer of mGlu2 contains an alpha chain and a beta chain. Occupation of both ECDs with the agonist, glutamate, is necessary for a fully active mGlu2<ref name="Du">Du, Juan, et al. “Structures of Human mglu2 and mglu7 Homo- and Heterodimers.” Nature News, Nature Publishing Group, 16 June 2021, https://www.nature.com/articles/s41586-021-03641-w.></ref>. However, only one chain in the dimer is responsible for activation of the G-protein, this suggests an asymmetrical signal transduction mechanism for mGlu2<ref name="Lin"/>. | mGlu2 is a [https://en.wikipedia.org/wiki/Protein_dimer homodimer]. Dimerization of mGlu2 is required to relay glutamate binding from the ECD to its transmembrane domain TMD. The homodimer of mGlu2 contains an alpha chain and a beta chain. Occupation of both ECDs with the agonist, glutamate, is necessary for a fully active mGlu2<ref name="Du">Du, Juan, et al. “Structures of Human mglu2 and mglu7 Homo- and Heterodimers.” Nature News, Nature Publishing Group, 16 June 2021, https://www.nature.com/articles/s41586-021-03641-w.></ref>. However, only one chain in the dimer is responsible for activation of the G-protein, this suggests an asymmetrical signal transduction mechanism for mGlu2<ref name="Lin"/>. | ||
===Inactive State=== | ===Inactive State=== | ||
A few hallmarks of the inactive structure of mGlu2 are the <scene name='90/904307/Better_inactive_structure/3'>Venus Fly Trap Domain (VFT)</scene> in the open conformation, well separated <scene name='90/904307/Better_inactive_structure/2'>Cysteine Rich Domain</scene>, and distinct orientation of the 7 Transmembrane Domains (7TM). The most critical component of the inactive form is the <scene name='90/904307/Tmd_helices/4'>asymmetric TM3-TM4 interface</scene> formed by the 7 α-helices in the α and β chains of the 7TM. The inactive structure of mGlu2 is mediated mainly by helices 3 and 4 on both the α and β chains of the dimer through hydrophobic interactions. These <scene name='90/904307/Tm3-tm4_hydrophobic/2'>hydrophobic interactions</scene> between both transmembrane helices stabilize inactive conformation of mGlu2<ref name="Lin"/>. Key hydrophobic interactions are between A630 V699 on the helix | A few hallmarks of the inactive structure of mGlu2 are the <scene name='90/904307/Better_inactive_structure/3'>Venus Fly Trap Domain (VFT)</scene> in the open conformation, well separated <scene name='90/904307/Better_inactive_structure/2'>Cysteine Rich Domain</scene>, and distinct orientation of the 7 Transmembrane Domains (7TM). The most critical component of the inactive form is the <scene name='90/904307/Tmd_helices/4'>asymmetric TM3-TM4 interface</scene> formed by the 7 α-helices in the α and β chains of the 7TM. The inactive structure of mGlu2 is mediated mainly by helices 3 and 4 on both the α and β chains of the dimer through hydrophobic interactions. These <scene name='90/904307/Tm3-tm4_hydrophobic/2'>hydrophobic interactions</scene> between both transmembrane helices stabilize inactive conformation of mGlu2<ref name="Lin"/>. Key hydrophobic interactions are between A630 V699 on the helix | ||
[[Image:Schematic of mGlu2.jpg|400 px|left|thumb|'''Figure 3.''' Demonstrates the conformational changes of mGlu2.]] | |||
===Intermediate Form=== | ===Intermediate Form=== | ||