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Metabotropic Glutamate Receptor

spinqualitylabelsall models Inactive Metabotropic Glutamate Receptor 2 PDB:7epa Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Figure 1. The coolest image of this protein EVAH!!! Metabotropic glutamate receptor Introduction Inactive mGlu2 Within the central nervous system (CNS), various receptors exist to detect extracellular molecules and thus communicate intracellularly. Found in eukaryotes and known for its seven transmembrane helices, one type of receptor is the G-protein coupled receptor (GPCR). The metabotropic glutamate receptor (mGlu), a Class C GPCR, is an essential receptor utilized in glutamate signaling. Eight different mGlu subtypes exist which are divided into three groups (I, II, III). While each mGlu has a slightly different function and location, the structures of the different mGlu subtypes are very similar (Table1). For each group, binding of the neurotransmitter glutamate to the mGlu introduces a conformational change that can activate a G protein. Group mGlu Type Location Function I mGlu1 mGlu5 Postsynaptic neurons Activates calcium channels Excites adenylyl cyclase II mGlu2 mGlu3 Presynaptic neurons Activates potassium channels Inhibits calcium channels Inhibits adenylyl cyclase III mGlu4 mGlu6 mGlu7 mGlu8 Presynaptic neurons Activates potassium channels Inhibits calcium channels Inhibits adenylyl cyclase Glutamate is an acidic, polar amino acid and is the main agonist involved in this transformation. (picture) This agonist binds to the extracellular portion of the protein allowing the homodimer to change conformationally. This change allows for a signaling cascade within the cell that can ultimately lead to the modification of other proteins and a difference in the synapse’s excitability. However, in mGlu, the binding affinity of glutamate is determined by either a positive (PAM) or negative (NAM) allosteric modulator. Structure Chains mGlu2 chains Domains mGlu2 domains Clinical Relevance Glutamate Bound Disease mGlu VFT

Active site interactions

Inactive mGlu

mGlu binding

Active mGlu

mGlu domains

mGlu chains

Glutamate in active site

Student Contributors

• Courtney Vennekotter
• Cade Chezem