Sandbox Reserved 1703: Difference between revisions

Transition to the active state also reorients helix 3 in both monomers to enable binding to the G-protein: Yet only one chain is required for full receptor activation. The intracellular region of helix 3 contributes the main interactions with the α-subunit of the G-protein. Intracellular Loop 2 also builds a polar interaction network with the G-protein through its ionic interactions with the <scene name='90/904308/Binding_recognition_site/2'> α-subunit</scene> of the G-protein. Lastly, mGlu2 residue E666 forms a salt bridge with residue (R32) on the α-subunit which further destabilizes the inactive conformation<ref name="Lin"/>.

The PAM induced downward shift of helix IV coupled with the reorientation of the transmembrane domain to a TM6-TM6 asymmetric interface, opens up a cleft on the intracellular surface of the receptor. This cleft allows a <scene name='90/904308/Hook_region/1'>hook-like region</scene>, from the last 4 terminals of the α-subunit of the G-protein, to move in adjacent to helix IV in the transmembrane domain. Within this interaction, <scene name='90/904308/Hook_region_recognition/2'>C351</scene> on the hook participates in hydrophobic interactions with Intracellular loop 2 and helix 4. These interactions allow the C-terminal region of the G-protein α-subunit to bind in the shallow groove formed by intracellular loops 2 and 3 and residues on helices 3 and lV<ref name="Lin" />.The receptor is now <scene name='90/904308/Active_structure/3'>fully active</scene> with the dimer coupled only to one G-protein. The ]VFT is in the closed conformation resulting in a tighter form. The TMD helices are also reoriented in both monomers to form an asymmetric dimer interface.